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Monographs

Radiopharmaceutical Preparations

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Radiopharmaceutical Preparations
Radiopharmaceutical Preparations comply with the requirements of the 3rd edition of the European
Pharmacopoeia [0125]. These requirements are reproduced below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITIONS
The statements of this monograph are intended to be read in conjunction with the monographs on
radiopharmaceutical preparations in the Pharmacopoeia.
For the purposes of this general monograph, radiopharmaceutical preparations cover:
radiopharmaceutical: any medicinal product which, when ready for use, contains one or more
radionuclides (radioactive isotopes) included for a medicinal purpose,
radionuclide generator: any system incorporating a fixed parent radionuclide from which is
produced a daughter radionuclide which is to be removed by elution or by any other method
and used in a radiopharmaceutical preparation.
kit for radiopharmaceutical preparation: any preparation to be reconstituted and/or combined
with radionuclides in the final radiopharmaceutical preparation, usually prior to its
administration,
radiopharmaceutical precursor: any other radionuclide produced for the radio-labelling of
another substance prior to administration.
A nuclide is a species of atom characterised by the number of protons and neutrons in its nucleus
(and hence by its atomic number Z, and mass number A) and also by its nuclear energy state.
Isotopes of an element are nuclides with the same atomic number but different mass numbers.
Nuclides containing an unstable arrangement of protons and neutrons will transform
spontaneously to either a stable or another unstable combination of protons and neutrons with a
constant statistical probability. Such nuclides are said to be radioactive and are called
radionuclides. The initial unstable nuclide is referred to as the parent radionuclide and the resulting
nuclide as the daughter nuclide.
The radioactive decay or transformation may involve the emission of charged particles, electron
capture (EC) or isometric transition (IT). The charged particles emitted from the nucleus may be
alpha particles (helium nucleus of mass number 4) or beta particles (negatively charged, generally
called electrons or positively charged, generally called positrons). The emission of charged
particles from the nucleus may be accompanied by the emission of gamma rays. Gamma rays are
also emitted in the process of isomeric transition. These emissions of gamma rays may be partly
replaced by the ejection of electrons known as internal conversion electrons. This phenomenon,
like the process of electron capture, causes a secondary emission of X-rays (due to the
reorganisation of the electrons in the atom). This secondary emission may itself be partly replaced
by the ejection of electrons known as Auger electrons. Radionuclides with a deficit of neutrons may
decay by emitting positrons. These radionuclides are called positron emitters. Positrons are
annihilated on contact with electrons, the process being accompanied by the emission of usually
two gamma photons, each with an energy of 511 keV, generally emitted at 180 to each other,
termed annihilation radiation.
The decay of a radionuclide is governed by the laws of probability with a characteristic decay
constant and follows an exponential law. The time in which a given quantity of a radionuclide
decays to half its initial value is termed the half-life (T).
The penetrating power of each radiation varies considerably according to its nature and its
energy. Alpha particles are completely absorbed in a thickness of a few micrometers to some tens
of micrometers of matter. Beta particles are completely absorbed in a thickness of several
millimetres to several centimetres of matter. Gamma rays are not completely absorbed but only
attenuated and a tenfold reduction may require, for example, several centimetres of lead. For most
absorbents, the denser the absorbent, the shorter the range of alpha and beta particles and the
greater the attenuation of gamma rays.
Each radionuclide is characterised by an invariable half-life expressed in units of time and by the
nature and energy of its radiation or radiations. The energy is expressed in electron-volts (eV), kiloelectronvolts (keV) or mega-electronvolts (MeV).
Generally the term radioactivity is used to describe the phenomenon of radioactive decay and
to express the physical quantity (activity) of this phenomenon. The radioactivity of a preparation is
the number of nuclear disintegrations or transformations per unit time.
In the International System (SI), radioactivity is expressed in becquerel (Bq) which is one
nuclear transformation per second. Absolute radioactivity measurements require a specialised
laboratory but identification and measurement of radiation can be carried out relatively by
comparing with standardised preparations provided by laboratories recognised by the competent
authority.

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Radionuclidic purity: the ratio, expressed as a percentage, of the radioactivity of the radionuclide
concerned to the total radioactivity of the radiopharmaceutical preparation. The relevant
radionuclidic impurities are listed with their limits in the individual monographs.
Radiochemical purity: the ratio, expressed as a percentage, of the radioactivity of the
radionuclide concerned which is present in the radiopharmaceutical preparation in the stated
chemical form, to the total radioactivity of that radionuclide present in the radiopharmaceutical
preparation. The relevant radiochemical impurities are listed with their limits in the individual
monographs.
Chemical purity: in monographs on radiopharmaceutical preparations chemical purity is
controlled by specifying limits on chemical impurities.
Isotopic carrier: a stable isotope of the element concerned either present or added to the radioactive preparation in the same chemical form as that in which the radionuclide is present.
Specific radioactivity: the radioactivity of a radionuclide per unit mass of the element or of the
chemical form concerned.
Radioactive concentration: the radioactivity of a radionuclide per unit volume.
Total radioactivity: the radioactivity of the radionuclide, expressed per unit (vial, capsule,
ampoule, generator, etc).
Starting materials: all the constituents which make up the radiopharmaceutical preparations.
Period of validity: the time during which specifications described in the monograph must be
fulfilled. Expiry date and, if necessary, time must be clearly stated.
PRODUCTION
A radiopharmaceutical preparation monograph describes as precisely as possible the method of
production of the radionuclide. A radiopharmaceutical preparations contains its radionuclide:
as an element in atomic or molecular form, e.g. [133Xe], [15O]O2,
as an ion, e.g. [131I] iodide, [99mTc]pertechnetate,
included in or attached to organic molecules by chelation, e.g. [111In]oxine or by covalent
bonding, e.g. 2-[18F]fluoro-2-deoxy-D-glucose.
The practical ways of producing radionuclides for use in, or as radiopharmaceutical preparations
are:
neutron bombardment of target materials (generally in nuclear reactors),
charged particles bombardment of target materials (in accelerators such as cyclotrons),
nuclear fission of heavy nuclides of target materials (generally after neutron or particle
bombardment),
from a radionuclide generator.
Neutron or charged particle bombardment
The nuclear reaction and the probability of its occurrence in unit time are dependent on the nature
and physical properties of the target material and the nature, energy and quantity of the incident
particles.
The nuclear transformation occurring through particle bombardment may be written in the
form:
target nucleus (bombarding particle, emitted particle or radiation) produced nucleus.
58Fe(n,g)59Fe
Examples:
18O(p,n)18F
In addition to the desired nuclear reaction adventitious transformations may occur. These will be
influenced by the energy of the incident particle and the purity of the target material. Such
adventitious transformations may give rise to radionuclidic impurities.
Nuclear fission
A small number of nuclides with a high atomic number are fissionable and the most frequently used
reaction is the fission of uranium-235 by neutrons in a nuclear reactor. Iodine-131, molybdenum99 and xenon-133 may be produced by nuclear fission of uranium-235. Their extraction from a
mixture of more than 200 other radionuclides must be carefully controlled in order to minimise the
radionuclidic impurities.
Radionuclide generators
Radionuclide generator systems use a relatively long-lived parent radionuclide which decays to a
daughter radionuclide, usually with shorter half-life.
By separating the daughter radionuclide from the parent radionuclide by a chemical or physical
process, it is possible to use the daughter at considerable distance from the production site of the
generators despite its short half-life.
Target materials
The isotopic composition and purity of the target material will determine the relative percentages of

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the principal radionuclide and radionuclidic impurities. The use of isotopically enriched target
material in which the abundance of the required target nuclide has been artificially increased, can
improve the production yield and the purity of the desired radionuclide.
The chemical form, the purity, the physical state and the chemical additives, as well as the
bombardment conditions and the direct physical and chemical environment will determine the
chemical state and chemical purity of the radionuclides which are produced.
In the production of radionuclides and particularly of short-lived radionuclides it may not be
possible to determine any of these quality criteria before further processing and manufacture of
radiopharmaceutical preparations. Therefore each batch of target material must be tested in test
production runs before its use in routine radionuclide production and manufacture of the radiopharmaceutical preparations, to ensure that under specified conditions, the target yields the
radionuclide in the desired quantity and quantity specified.
The target material is contained in a holder in gaseous, liquid or solid state in order to be
irradiated by a beam of particles. For neutron bombardment, the material is commonly contained
in quartz ampoules or high purity aluminium or titanium containers. It is necessary to ascertain that
no interaction can occur between the container and its contents under the irradiation conditions
(temperature, pressure, time).
For charged particle bombardment, the holder for target material is usually built of aluminium or
another appropriate metal, with inlet and outlet ports, a surrounding cooling system and usually a
thin metal foil target window. The nature and thickness of the target window have a particular
influence on the yield of the nuclear reaction and may also affect the radionuclidic purity.
The production procedure clearly describes:
target material,
construction of the holder for target material,
loading of target material into the irradiation system,
method of irradiation (bombardment),
separation of the desired radionuclide,
and evaluates all effects on the efficiency of the production in terms of quality and quantity of the
produced radionuclide.
The chemical state of the isolated radionuclide may play a major role in all further processing.
Precursors for synthesis
Generally, these precursors are not produced on a large scale. Some precursors are synthesised by
the radiopharmaceutical production laboratory, others are supplied by specialised producers or
laboratories.
Test for identity, for chemical purity and the assay must be performed by validated procedures.
When batches of precursors are accepted using data from the certificates of analysis, suitable
evidence has to be established to demonstrate the consistent reliability of the suppliers analyses
and at least one identity test must be conducted. It is recommended to test precursor materials in
production runs before their use for the manufacture of radiopharmaceutical preparations, to
ensure that under specified production conditions, the precursor yields the radiopharmaceutical
preparation in the desired quantity and quality specified.
Performance of the production system
All operations, from the preparation of the target to the dispensing of the final radiopharmaceutical
preparation, must be clearly documented including their impact on the purity of the final product
and the efficiency of the procedure. Where possible, in-process controls are performed and the
results recorded at each production step to identify at which level a possible discrepancy from the
normal production pathway may have occurred.
a) The production of radiopharmaceutical preparations may make use of mechanical and
automated processes that are used in the pharmaceutical industry, subject to adapting these
to the specificity of the radioactive starting material and to the requirements of
radioprotection.
b) For radiopharmaceutical preparations containing short-lived radionuclides, such as certain
positron emitters, remotely controlled production and automated radiosynthesis are
generally used. For radionuclides with a very short half-life (less than 20 min) the control of
the performance of the production system is an important measure to assure the quality of
the radiopharmaceutical preparation before its release.
c) Any production procedure must be validated in test production runs before its use in routine
manufacture of radiopharmaceutical preparations, to ensure that under specified production
conditions, the production system yields the radiopharmaceutical preparation in the desired
quantity and specified quality.
d) The preparation of the dosage form of the final radiopharmaceutical preparation in the
practice of nuclear medicine generally involves limited radioactivity starting from ready-to-

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use radiopharmaceutical preparations, generators, kits and radioactive precursors. All
conditions which may affect the quality of the product (e.g. radiochemical purity and
sterility) must be clearly defined and must include appropriate measures for radiation
protection.
IDENTIFICATION
Radioactive decay: radioactivity decays at an exponential rate with a decay constant characteristic
of each radionuclide.
The curve of exponential decay (decay curve) is described by the equation:
At = A e t
A t = the radioactivity at time t,
Ao = the radioactivity at time t = 0,
l= the decay constant characteristic of each radionuclide
e = the base of Napierian logarithms.
The half-life (T) is related to the decay constant (l) by the equation:
T =

ln 2

(ln 2

0.693)

The radionuclide is generally identified by its half-life or by the nature and energy of its radiation or
radiations or by both, as prescribed in the monograph.
Measurement of half-life. The half-life is measured with a suitable detection apparatus such as an
ionisation chamber, a Geiger-Mller counter, a scintillation counter (solid crystal, liquid) or a
semiconductor detector. The preparation to be tested is used as such or diluted or dried in a
capsule after appropriate dilution. The radioactivity chosen, having regard to experimental
conditions, must be of a sufficiently high level to allow detection during several estimated half-lives,
but not too high to minimise count rate losses, for example due to dead time.
The radioactive source is prepared in a manner that will avoid loss of material during handling. If
it is a liquid (solution), it is contained in bottles or sealed tubes. If it is a solid (residue from drying
in a capsule), it is protected by a cover consisting of a sheet of adhesive cellulose acetate or of some
other material.
The same source is measured in the same geometrical conditions and at intervals usually corresponding to half of the estimated half-life throughout a time equal to about three half-lives. The
correct functioning of the apparatus is checked using a source of long half-life and, if necessary,
corrections for any changes of the count rate have to be applied (see Measurement of Radioactivity).
A graph can be drawn with time as the abscissa and the logarithm of the relative instrument
reading (e.g. count rate) as the ordinate. The calculated half-life differs by not more than 5 per
cent from the half-life stated in the Pharmacopoeia, unless otherwise stated.
Determination of the nature and energy of the radiation The nature and energy of the
radiation emitted may be determined by several procedures including the construction of an
attenuation curve and the use of spectrometry. The attenuation curve can be used for analysis of
electron radiation; spectrometry is mostly used for identification of gamma rays and detectable Xrays.
The attenuation curve is drawn for pure electron emitters when no spectrometer for beta rays is
available or for beta/gamma emitters when no spectrometer for gamma rays is available. This
method of estimating the maximum energy of beta radiation gives only an approximate value. The
source, suitably mounted to give constant geometrical conditions, is placed in front of thethin
window of a Geiger-Mller counter or a proportional counter. The source is protected as
described above. The count rate of the source is then measured. Between the source and the
counter are placed, in succession, at least six aluminium screens of increasing mass per unit area
within such limits that with a pure beta emitter this count rate is not affected by the addition of
further screens. The screens are inserted in such a manner that constant geometrical conditions
are maintained. A graph is drawn showing, as the abscissa, the mass per unit area of the screen
expressed in milligrams per square centimeter and, as the ordinate, the logarithm of the count rate
for each screen examined. A graph is drawn in the same manner for a standardised preparation.
The mass attenuation coefficients are calculated from the median parts of the curves, which are
practically rectilinear.
The mass attenuation coefficient m, expressed in square centimetres per milligram, depends on the
energy spectrum of the beta radiation and on the nature and the physical properties of the screen.
It therefore allows beta emitters to be identified. It is calculated using the equation:

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m =

ln A1 ln A2
m2 m1

m1 = mass per unit area of the lightest screen,


m2 = mass per unit area of the heaviest screen, m1 and m2 being within the rectilinear part of
the curve,
A1 = count rate for mass per unit area m1,
A2 = count rate for mass per unit area m2.
The mass attenuation coefficient m thus calculated does not differ by more than 10 per cent from
the coefficient obtained under identical conditions using a standardised preparation of the same
radionuclide.
The range of beta particles is a further parameter which can be used for the determination of the
beta energy. It is obtained from the graph described above as the mass per unit area corresponding
to the intersection of the extrapolations of the descending rectilinear part of the attenuation curve
and the horizontal line of background radioactivity.
Liquid scintillation counting may be used to obtain spectra of a- and b-emitters (see measurement of
radioactivity).
Gamma spectrometry is used to identify radionuclides by the energy and intensity of their gamma rays
and X-rays.
The preferred detector for gamma and X-ray spectrometry is a germanium semiconductor
detector. A thallium-activated sodium iodide scintillation detector is also used but this has a much
lower energy resolution.
The gamma detector has to be calibrated using standard sources because the detection efficiency
is a function of the energy of the gamma and X-rays as well as the form of the source and the
source-to-detector distance. The detection efficiency may be measured using a calibrated source of
the radionuclide to be measured or, for more general work, a graph of efficiency against gamma
and X-ray energy may be constructed from a series of calibrated sources of various radionuclides.
The gamma and X-ray spectrum of a radionuclide which emits gamma and X-rays is unique to
that nuclide and is characterised by the energies and the number of photons of particular energies
emitted per transformation from one energy level to another energy level. This property
contributes to the identification of radionuclides present in a source and to their quantification. It
allows the estimation of the degree of radionuclidic impurity by detecting peaks other than those
expected.
It is possible to establish the rate of the decay of radioactivity using gamma spectrometry since
the peaks diminish in amplitude as a function of the half-life. If, in such a source, a radioactive
impurity with a different half-life is present, it is possible to detect the latter by identification of the
characteristic peak or peaks whose amplitudes decrease at a different rate from that expected for
the particular radionuclide. A determination of the half-life of the additional peaks by repeated
measurements of the sample will help to identify the impurity.
The Table of physical characteristics of radionuclides mentioned in the European Pharmacopoeia (5.7)
(reproduced at the end of this monograph) summarises the most commonly accepted physical
characteristics of radionuclides used in preparations which are the subject of monographs in the
European Pharmacopoeia. In addition, the Table states the physical characteristics of the main
potential impurities of the radionuclides mentioned in the monographs.
By transition probability is meant the probability of the transformation of a nucleus in a given
energy state, via the transition concerned. Instead of probability the terms intensity and
abundance are frequently used.
By emission probability is meant the probability of an atom of a radionuclide giving rise to the
emission of the particles or radiation concerned.
Irrespective of whether the one or the other meaning is in intended, probability is usually
measured in terms of 100 disintegrations.
MEASUREMENT OF RADIOACTIVITY
The radioactivity of a preparation is stated at a given date and, if necessary, time.
The absolute measurement of the radioactivity of a given sample may be carried out if the decay
scheme of the radionuclide is known, but in practice many corrections are required to obtain
accurate results. For this reason it is common to carry out the measurement with the aid of a
primary standard source. Primary standards may not be available for short-lived radionuclides e.g.
positron emitters. Measuring instruments are calibrated using suitable standards for the particular
radionuclides. Standards are available from the laboratories recognised by the competent
authority. Ionisation chambers and Geiger-Mller counters may be used to measure beta and beta/
gamma emitters; scintillation or semiconductor counters or ionisation chambers may be used for
measuring gamma emitters; low-energy beta emitters require a liquid-scintillation counter. For the
detection and measurement of alpha emitters, specialised equipment and techniques are required.

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For an accurate comparison of radioactive source, it is essential for samples and standards to be
measured under similar conditions.
Low-energy beta emitters may be measured by liquid-scintillation counting. The sample is
dissolved in a solution containing one or more often two organic fluorescent substances (primary
and secondary scintillators), which convert part of the energy of disintegration into photons of
light, which are detected by a photomultiplier and converted into electrical impulses. When using a
liquid-scintillation counter, comparative measurements are corrected for light-quenching effects.
Direct measurements are made, wherever possible, under similar condition, (e.g. volumes and type
of solutions) for the source to be examined and the standard source.
All measurements of radioactivity must be corrected by subtracting the background due to the
radioactivity in the environment and to spurious signals generated in the equipment itself.
With some equipment, when measurements are made at high levels of radioactivity, it may be
necessary to correct for loss by coincidence due to the finite resolving time of the detector and its
associated electronic equipment. For a counting system with a fixed dead time t following each
count, the correction is:

N =

Nobs
1 Nobs

N = the true count rate per second,


Nobs = the observed count rate per second,
t= the dead time in seconds.
With some equipment this correction is made automatically. Corrections for loss by coincidence
must be made before the correction for background radiation.
If the time of an individual measurement, tm is not negligibly short compared with the half-life,
T, the decay during this measurement time must be taken into account. After having corrected the
instrument reading (count rate, ionisation current, etc.) for background and, if necessary, for
losses due to electronic effects, the decay correction during measurement time is:
R

R corr =

t m ln2

T
t m ln2

1 exp
T

Rcorr = instrument reading corrected to the beginning of the individual measurement,


R = instrument reading before decay correction, but already corrected for background, etc.
The results of determinations of radioactivity show variations which derive mainly from the random
nature of nuclear transformation. A sufficient number of counts must be registered in order to
compensate for variations in the number of transformations per unit of time. The standard
deviation is the square root of the counts, so at least 10,000 counts are necessary to obtain a
relative standard deviation of not more than 1 per cent (confidence interval: 1 sigma).
All statements of radioactive content are accompanied by a statement of the date and, if
necessary, the time at which the measurement was made. This statement of the radioactive content
must be made with reference to a time zone (GMT, CET). The radioactivity at other times may be
calculated from the exponential equation or from tables.
The radioactivity of a solution is expressed per unit volume to give the radioactive concentration.
RADIONUCLIDIC PURITY
In most of the cases, to state the radionuclidic purity of a radiopharmaceutical preparation, the
identity of every radionuclide present and their radioactivity must be known. The most generally
useful method for examination of radionuclidic purity is that of gamma spectrometry. It is not a
completely reliable method because alpha- and beta-emitting impurities are not usually easily
detectable and, when sodium iodide detectors are employed, the peaks due to gamma emitting
impurities are often obscured by the spectrum of the principal radionuclide.
The individual monographs prescribe the radionuclidic purity required (for example, the gammaray spectrum does not significantly differ from that of a standardised preparation) and may set
limits for specific radionuclidic impurities (for example, cobalt-60 in cobalt-57). While these
requirements are necessary, they are not in themselves sufficient to ensure that the radionuclidic
purity of a preparation is sufficient for human use. The manufacturer must examine the product in
detail and especially must examine preparations of radionuclides of short half-life for impurities of
long half-life after a suitable period of decay. In this way, information on the suitability of his
manufacturing processes and the adequacy of the testing procedures may be obtained. In cases
where two or more positron emitting radionuclides need to be identified and/or differentiated, as
e.g. 18F-impurities in 13N-preparations, half-life determinations need to be carried out in addition to
gamma spectrometry.

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Due to differences in the half-lives of the different radionuclides present in a radiopharmaceutical
preparation, the radionuclidic purity changes with time. The requirement of the radionuclidic
purity must be fulfilled throughout the period of validity. It is sometimes difficult to carry out these
tests before authorising the release for use of the batch when the half-life of the radionuclide in the
preparation is short. The test then constitutes a control of the quality of production.
RADIOCHEMICAL PURITY
The determination of radiochemical purity requires separation of the different chemical substances
containing the radionuclide and estimating the percentage of radioactivity associated with the
declared chemical substance. Radiochemical impurities may originate from:
radionuclide production,
subsequent chemical procedures,
incomplete preparative separation,
chemical changes during storage.
The requirement of the radiochemical purity must be fulfilled throughout the period of validity.
In principle, any method of analytical separation may be used in the determination of
radiochemical purity. For example, the monographs for radiopharmaceutical products may include
paper chromatography (2.2.26), thin-layer chromatography (2.2.27), electrophoresis (2.2.31), sizeexclusion chromatography (2.2.30), gas chromatography (2.2.28) and liquid chromatography
(2.2.29). The technical description of these analytical methods is set out in the monographs.
Moreover certain precautions special to radioactivity must also be taken for radiation protection.
In a hospital environment thin-layer and paper chromatography are mostly used. In paper and
thin-layer chromatography, a volume equal to that described in the monograph is deposited on the
starting-line as prescribed in the general methods for chromatography. It is preferable not to dilute
the preparation to be examined but it is important to avoid depositing such a quantity of radioactivity that counting losses by coincidence occur during measurement of the radioactivity. On account
of the very small quantities of the radioactive material applied, a carrier may be added when
specified in a particular monograph. After development, the support is dried and the positions of
the radioactive areas are detected by autoradiography or by measurement of radioactivity over the
length of the chromatogram, using suitable collimated counters or by cutting the strips and
counting each portion. The positions of the spots or areas permit chemical identification by
comparison with solutions of the same chemical substances (non-radioactive) using a suitable
detection method.
Radioactivity may be measured by integration using an automatic-plotting instrument or a digital
counter. The ratios of the areas under the peaks give the ratios of the radioactive concentration of
the chemical substances. When the strips are cut into portions, the ratios of the quantities of
radioactivity measured give the ratio of concentrations of the radioactive chemical species.
SPECIFIC RADIOACTIVITY
Specific radioactivity is usually calculated taking into account the radioactive concentration (radioactivity per unit volume) and the concentration of the chemical substance being studied, after
verification that the radioactivity is attributable only to the radionuclide (radionuclidic purity) and
the chemical species (radiochemical purity) concerned.
Specific radioactivity changes with time. The statement of the specific radioactivity therefore
includes reference to a date and, if necessary, time. The requirement of the specific radioactivity
must be fulfilled throughout the period of validity.
CHEMICAL PURITY
The determination of chemical purity requires quantification of the individual chemical impurities
specified in the monograph.
ENANTIOMERIC PURITY
Where appropriate, the stereoisomeric purity has to be verified.
PHYSIOLOGICAL DISTRIBUTION
A physiological distribution test is prescribed, if necessary, for certain radiopharmaceutical preparations. The distribution pattern of radioactivity observed in specified organs, tissues or other body
compartments of an appropriate animal species (usually rats or mice) can be a reliable indication of
the expected distribution in humans and thus of the suitability for the intended purpose.
The individual monograph prescribes the details concerning the performance of the test and the
physiological distribution requirements which must be met for the radiopharmaceutical preparation. A physiological distribution conforming to the requirements will assure appropriate
distribution of the radioactive compounds to the intended biological target in humans and limits its
distribution to non-target areas.
In general, the test is performed as follows.
Each of three animals is injected intravenously with the preparation to be tested. If relevant, the
species, sex, strain and weight and/or age of the animals is specified in the monograph. The test

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injection is the radiopharmaceutical preparation as it is intended for human use. Where applicable,
products are reconstituted according to the manufacturers instructions. In some cases, dilution
immediately before injection may be necessary.
The administration will normally be made via the intravenous route for which purpose the caudal
vein is used. Other veins such as the saphenous, femoral, jugular or penile veins may be used in
special cases. Animals showing evidence of extravasation of the injection (observed at the time of
injection or revealed by subsequent assay of tissue radioactivity are rejected from the test.
Immediately after injection each animal is placed in a separate cage which will allow collection of
excreta and prevent contamination of the body surface of the animal.
At the specified time after injection, the animals are killed by an appropriate method and
dissected. Selected organs and tissues are assayed for their radioactivity using a suitable instrument
as described elsewhere in this monograph. The physiological distribution is then calculated and
expressed in terms of the percentage of the radioactivity which is found in each of the selected
organs or tissues. For this purpose the radioactivity in an organ may be related to the injected
radioactivity calculated from the radioactive content of the syringe measured before and after
injection. For some radiopharmaceutical preparations it may be appropriate to determine the ratio
of the radioactivity in weighed samples of selected tissues (radioactivity/mass).
For a preparation to meet the requirements of the test, the distribution of radioactivity in at least
two of the three animals must comply with all the specified criteria.
STERILITY
Radiopharmaceutical preparations for parenteral administration must be prepared using
precautions designed to exclude microbial contamination and to ensure sterility. The test for
sterility is carried out as described in the general method for sterility (2.6.1). Special difficulties
arise with radiopharmaceutical preparations because of the short half-life of some radionuclides,
small size of batches and the radiation hazards. It is not always possible to await the results of the
test for sterility before authorisation of the release for use of the bath concerned. Parametric
release (5.1.1) of the product manufactured by a fully validated process is the method of choice in
such cases. When aseptic manufacturing is used, the test for sterility has to be executed as a control
of the quality of production.
When the size of a batch of the radiopharmaceutical preparation is limited to one or a few
samples (e.g. therapeutic or very short-lived radiopharmaceutical preparation), sampling the batch
for sterility testing may not be applicable. If the radiopharmaceutical preparation is sterilised by
filtration and/or aseptically processed (5.1.1) process validation is critical.
When the half-life of the radionuclide is very short (e.g. less than 20 min), the administration of
the radiopharmaceutical preparation to the patient is generally on-line with a validated production
system.
For safety reasons (high level of radioactivity) it is not possible to use the radiopharmaceutical
preparations as required in the test for sterility (2.6.1). The method by membrane filtration is to be
preferred to limit irradiation of personnel.
Notwithstanding the requirements concerning the use of antimicrobial preservatives in Parenteral
preparations (0520), their addition to radiopharmaceutical preparations in multidose container is not
obligatory, unless prescribed in the monograph.
BACTERIAL ENDOTOXINSPYROGENS
For certain radiopharmaceutical preparations a test for bacterial endotoxins is prescribed. The test
is carried out as described in the general method (2.6.14), taking the necessary precautions to limit
irradiation of the personnel carrying out the test.
The limit for bacterial endotoxins is indicated in the individual monograph.
When the nature of the radiopharmaceutical preparation results in an interference by inhibition
or activation and it is not possible to eliminate the interfering factor(s), the test for pyrogens (2.6.8)
may be specifically prescribed.
It is sometimes difficult to carry out these tests before releasing the batch for use when the halflife of the radionuclide in the preparation is short. The test then constitutes a control of the quality
of production.
STORAGE
Store in an airtight container in a place that is sufficiently shielded to protect personnel from
irradiation by primary or secondary emissions and that complies with national and international
regulations concerning the storage of radioactive substances. During storage, containers may
darken due to irradiation. Such darkening does not necessarily involve deterioration of the preparations.
Radiopharmaceutical preparations are intended for use within a short time and the end of
the period of validity must be clearly stated.
LABELLING

70-10
The labelling of radiopharmaceutical preparations complies with the relevant national and
European legislation.
The label on the direct container states:
the name of the preparation and/or its reference,
the name of the manufacturer,
an identification number,

70-11
for liquid and gaseous preparations: the total radioactivity in the container, or the radioactive
concentration per millilitre at a stated date and, if necessary, time, and the volume of liquid on
the container,
for solid preparations (such as freeze-dried preparations): the total radioactivity at a stated
date and, if necessary, time. After reconstitution with the appropriate solution, the preparation is considered as a liquid preparation,
for capsules: the radioactivity per capsule at a stated date and, if necessary, time and the
number of capsules in the container.
The labelling can be adapted in certain cases (e.g. radiopharmaceutical preparations containing
short-lived radio-nuclides.
In addition, the label on the outer package states:
the route of administration,
the period of validity or the expiry date,
the name and concentration of any added antimicrobial preservative,
where applicable, any special storage conditions.
__________________________________________________________________________________________________________ Ph Eur

Table of Physical Characterisitics of Radionuclides Mentioned in the


European Pharmacopoeia
The following table is given to complete the general monograph on Radiopharmaceutical Preparations
(0125).
The values are obtained from the database of the National Nuclear Data Center (NNDC) at
Brookhaven National Laboratory, Upton. N.Y., USA, directly accessible via Internet at the
address:
http://www.nndc.bnl.gov/nndc/nudat/radform.html.
In case another source of information is preferred (more recent values), this source is explicitly
mentioned.
Other data sources:
* DAMRI (Dpartement des Applications et de la Mtrologie des Rayonnements Ionisants,
CEA Gif-sur-Yvette, France),
** PTB (Physikalisch-Technische Bundesanstalt, Braunschweig, Germany),
*** NPL (National Physical Laboratory, Teddington, Middlesex, UK).
The uncertainty of the half-lives are given in parentheses. In principle the digits in parentheses are
the standard uncertainty of the corresponding last digits of the indicated numerical value Guide to
the Expression of Uncertainty in measurement, International Organisation for Standardisation (ISO),
1993, ISBN 92-67-10188-9).
The following abbreviations are used:
eA = Auger electrons
ce = conversion electrons
b = electrons
b+ = positrons

70-12
g = gamma rays
X = X-rays
Radionuclide

Half-life

Electron emission

Photon emission

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

Tritium (3H)

*12.33 (6)
years

*0.006 (I)
(max: 0.019)

*100

Carbon-11 (11C)

20.385 (20)
min

0.386 (I)
(max: 0.960)

99.8

0.511

199.5(II)

Nitrogen-13 (13N)

9.965 (4) min

0.492(I)
1.198)

99.8

0.511

199.6(II)

(max:

Oxygen-15 (15O)

122.24 (16) s

0.735 (I)
(max: 1.732)

99.9

0.511

199.8(II)

Fluorine-18 (18F)

109.77 (5)
min

0.250 (I)
(max: 0.633)

96.7

0.511

193.5(II)

Phosphorus-32 (32P)

14.26 (4)
days

0.695 (I)
(max: 1.71)

100

Phosphorus-33 (33P)

25.34 (12) days

0.076 (I)
(max: 0.249)

100

Sulphur-35 (35S)

87.51 (12) days

0.049 (I)
(max: 0.167)

100

Chromium-51 (51Cr)

27.7025 (24)
days

eA

0.004

67

0.005

22.3

Cobalt-56

(I) Mean

(56Co)

77.27 (3 days)

0.320

9.9

eA

0.006

47

0.006-0.007

25

0.179 (I)

0.9

0.511

38.0(II)

0.631 (I)

18.1

0.847
1.038
1.175
1.238
1.360
1.771
2.015
2.035
2.598
3.202
3.253

100.0
14.1
2.2
66.1
4.3
15.5
3.0
7.8
17.0
3.1
7.6

energy of the spectrum.

(II) Maximum

emission probability corresponding to a total annihilation in the source per 100 disintegrations.

70-13
Radionuclide

Half-life

Cobalt-57 (57Co)

Cobalt-58 (58Co)

Cobalt-60 (60Co)
Gallium-66 (66Ga)

Gallium-67 (67Ga)

271.79 (9) days

70.86 (7) days

Electron emission

Photon emission

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

eA+ ce

0.006-0.007

177.4

0.006-0.007

57

ce

0.014
0.115
0.129

7.4
1.8
1.3

0.014
0.122
0.136
0.692

9.2
85.6
10.7
0.15

eA

0.006

49.4

0.006-0.007

26.3

0.201 (I)

14.9

0.511
0.811
0.864
1.675

29.9(II)
99.4
0.7
0.5

0.096(I)

99.9

1.173
1.333

100.0
100.0

5.2714 (5)
years

9.49 (7) hours

eA

0.008

21

0.009-0.010

19.1

0.157(I)
0.331(I)
0.397(I)
0.782(I)
1.90(I)

1
0.7
3.8
0.3
50

0.511
0.834
1.039
1.333
1.919
2.190
2.423
2.752
3.229
3.381
3.792
4.086
4.295
4.807

112(II)
5.9
37
1.2
2.1
5.6
1.9
23.4
1.5
1.5
1.1
1.3
4.1
1.8

eA

0.008

62

0.008-0.010

57

ce

0.082-0.084
0.090-0.092
0.175

30.4
3.6
0.3

0.091-0.093
0.185
0.209
0.300
0.394
0.888

42.4
21.2
2.4
16.8
4.7
0.15

eA

0.008

42.4

0.009-0.010

44.1

0.353(I)

1.2
88.0

0.836(I)

0.511
1.077

178.3
3.0

3.2612 (6) days

(max: 0.318)

Germanium-68 (68Ge)
in equilibrium with
Gallium-68 (68Ga)

270.82 (27)
days

Gallium-68 (68Ga)

67.629 (24)
min

eA

0.008

5.1

0.009-0.010

4.7

0.353(I)
0.836(I)

1.2
88.0

0.511
1.077

178.3
3.0

13.10 (3) s

ce

0.176
0.189

26.4
4.6

0.012-0.014

17.0

0.190

67.6

eA

0.011

31.3

0.013-0.014

57.2

ce

0.176
0.188

25.0
4.3

0.253(I)
0.447(I)

1.8
25.0

0.190
0.446
0.457
0.510
0.511
0.538

64
23.2
3.0
5.3
54.2
2.2

Krypton-81m (81Kr)
Rubidium-81 (91Rb) in
equilibrium with
Krypton-81m (91mKr)

(68Ga: 67.629
(24) min)

4.576 (5) hours

(91mKr: 13.10
(3) s)
(I)Mean

energy of the spectrum.

(II)Maximum

emission probability corresponding to a total annihilation in the source per 100 disintegrations.

70-14
Radionuclide

Half-life

Electron emission

Strontium-89 (89Sr)
in equilibrium with
Yttrium-89m (89Y)

50.53 (7) days

Strontium-90 (90Sr)
in equilibrium with
Yttrium-90 (90Y)

28.74 (4) years

90

Photon emission

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

0.583(I)
(max: 1.492)

99.99

0.909

0.01

0.196(I)
(max: 0.546)

100

89Y:

16.06
(
(4) s)
(90Y: 64.10 (8)
hours)

Yttrium-90 ( Y)

64.10 (8)
hours

0.934(I)
(max: 2.280)

100

Molybdenum-99
99
( Mo) in equilibrium
with Technetium-99m
99m
( Tc)

65.94 (1) hours

0.133(I)
0.290(I)
0.443(I)

16.4
(I)
1.1
(I)
82.4

0.018-0.021

3.6

0.041
0.141
0.181
0.366
0.740
0.778

1.1
4.5
6
1.2
12.1
4.3

ce

0.002

74

0.018-0.021

7.3

eA

0.015

2.1

0.141

89.1

ce

0.120
0.137-0.140

9.4
1.3

0.085(I)
(max: 0.294)

100

eA+ ce

0.017

12

0.020-0.023

9.0

ce

0.030-0.039

88.3

0.497
0.610

91
5.8

(I)

(99mTc: 6.01
(1) hours)

Technetium-99m
(99mTc)

6.01 (1) hours

Technetium-99 (99Tc)

2.11 10
years

Ruthenium-103
(103Ru) in equilibrium
with Rhodium-103m
(103mRh)

39.26 (2) days

110

Indium-110 ( In)

Indium-110m (110mIn)

111

Indium-111 ( In)

Indium-114m (114mIn)
in equilibrium with
Indium-114 (114In)

(I)Mean

103mRh:

(
56.114 (20)
min)

4.9 (1) hours

eA

69.1 (5) min

2.8047 (5) days

(I)

(I)

0.031
0.064(I)

6.6
(I)
92.2

0.019

13.4

0.023-0.026

70.5

0.642
0.658
0.885
0.938
0.997

25.9
98.3
92.9
68.4
10.5
27.8

eA

0.019

5.3

0.023-0.026

1.015(I)

61

0.511
0.658
2.129

123.4(II)
97.8
2.1

eA

0.019

15.6

0.003
0.023-0.026

6.9
82.3

ce

0.145

7.8

0.167-0.171
0.219
0.241-0.245

1.3
4.9
1.0

0.171
0.245

90.2
94.0

0.023-0.027

36.3

0.190
0.558
0.725

15.6
3.2
3.2

49.51 (1) days

ce

0.162
0.186-0.190

40
40

(114In: 71.9
(1) s)

0.777(I)
(max: 1.985)

95

(I)

energy of the spectrum.

(II)Maximum

emission probability corresponding to a total annihilation in the source per 100 disintegrations.

70-15
Radionuclide

Half-life

Tellurium-121m
(121mTe) in equilibrium
with Tellurium121(121Te)

Tellurium-121 (121Te)

Iodine-123 (123I)

Iodine-125 (125I)

Iodine-126

(126I)

Electron emission

Photon emission

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

eA

0.003
0.022-0.023

88.0
7.4

0.026-0.031

50.5

ce

0.050
0.077
0.180

33.2
40.0
6.1

0.212
1.102

81.4
2.5

**19.16 (5)
days

eA

0.022

11.6

0.026-0.030

75.6

0.470
0.508
0.573

1.4
17.7
80.3

13.27 (8) hours

eA

0.023

12.3

0.004
0.027-0.031

9.3
86.6

ce

0.127
0.154
0.158

13.6
1.8
0.4

0.159
0.346
0.440
0.505
0.529
0.538

83.3
0.1
0.4
0.3
1.4
0.4

eA + ce

0.004
0.023-0.035

80
33

0.004
0.027
0.031

15.5
114
26

0.035

6.7

0.0270.031
0.388
0.491
0.511(x)
0.666(x)
0.754(x)
0.880(x)
1.420(x)

42.2
34
2.9
2.3(II)
33(x)
4.2(x)
0.8(x)
0.3(x)

0.029-0.030

3.9

0.080
0.284
0.365
0.637
0.723

2.6
6.1
81.7
7.2
1.8

154.0 (7) days


(121Te:

19.16
(5) days)

59.402 (14)
days

13.11 (5) days

eA

0.023
0.354
0.634

6
0.5
0.1

+
b(
b(

0.109(I)
0.290(I)
0.459(I)

3.6(x)
32.1(x)
8.0(x)

0.530(I)

ce

0.46
0.330

3.5
1.6

0.069(I)
0.097(I)
0.192(I)

2.1
7.3
89.9

eA

0.025

6.8

ce

0.129
0.159
0.163

61
28.5
8.3

0.004
0.030
0.034

8.3
44.0
10.2

0.164

2.0

Iodine-131 (131I)

Xenon-131m (131mXe)

8.02070 (11)
days

11.84 (7) days

Iodine-133 (133I)
(decays to radioactive
Xenon-133)

20.8 (1) hours

0.140(I)
0.162(I)
0.299(I)
0.441(I)

3.8
3.2
4.2
83

0.530
0.875
1.298

87
4.5
2.4

Xenon-133 (133Xe)

5.243 (1) days

eA

0.026

5.8

ce

0.045
0.075-0.080

55.1
9.9

0.004
0.031
0.035

6.3
40.3
9.4

0.080

38.3

0.101(I)

99.0

(I)Mean

(I)

energy of the spectrum.

(II)Maximum

emission probability corresponding to a total annihilation in the source per 100 disintegrations.

70-16
Radionuclide

Half-life

Xenon-133m (133mXe)
(decays to radioactive
Xenon-133)

2.19 (1) days

Iodine-135
(135I)(decays to
radioactive Xenon-135)

6.57 (2) hours

Xenon-135 (135Xe)

9.14 (2) hours

Caesium-137 (137Cs) in
equilibrium with
Barium-137m (137mBa)

Thallium-200 (200Tl)

30.04 (3) years

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

eA

0.025

ce

0.199
0.228
0.232

64.0
20.7
4.6

0.004
0.030
0.034

7.8
45.9
10.6

0.233

0.140(I)

7.4(I)

0.237(I)
0.307(I)
0.352(I)
0.399(I)
0.444(I)
0.529(I)

8(I) (I
8.8(I) (
21.9(I)
8(I)
7.5(I)
23.8(I)

*0.527
0.547(I)
0.837(I)
1.039(I)
1.132(I)
1.260(I)
1.458(I)
1.678(I)
1.791(I)

13.8(I)
7.2(I)
6.7(I)
8.0(I)
22.7(I)
28.9(I)
8.7(I)
9.6(I)
7.8(I)

ce

0.214

5.5

0.031-0.035

5.0

0.171
0.308

3.1
96.0

0.250
0.608

90.2
2.9

eA

0.026

0.8

ce

0.624
0.656

8.0
1.4

0.005
0.032-0.036

1
7

0.662

85.1

0.010
0.069-0.071
0.08

32.0
63.3
17.5

0.368
0.579
0.828
1.206
1.226
1.274
1.363
1.515

87.2
13.8
10.8
29.9
3.4
3.3
3.4
4.0

26.1 (1) hours

Thallium-201 (201Tl)

72.912 (17)
hours

(I)Mean

Emission
probability
(per 100
disintegrations)

9.33 (3) hours

12.23 (2) days

Photon emission

Energy (MeV)

(137mBa: 2.552
(1) min)

Lead-201 (201Pb)
(decays to radioactive
Thallium-201)

Thallium-202 (202Tl)

Electron emission
Type

(I)

(I)

0.174
0.416(I)

94.4
(I)
5.6

ce

0.285
0.353

3.4
1.4

0.495(I)

0.3

(I)

eA

0.055

ce

0.246
0.276
0.316

8.5
2
2.3

0.070-0.073
0.083

69
19

0.331
0.361
0.406
0.585
0.692
0.767
0.826
0.908
0.946
1.099
1.277

79
9.9
2.0
3.6
4.3
3.2
2.4
5.7
7.9
1.8
1.6

0.016-0.017
0.027-0.029
0.052
0.084
0.153

17.7
4.1
7.2
15.4
2.6

0.010
0.069-0.071
0.080

46.0
73.7
20.4

0.135
0.167

2.6
10.0

eA

0.054

2.8

ce

0.357

2.4

0.010
0.069-0.071
0.080

31.0
61.6
17.1

0.440

91.4

ce

energy of the spectrum.

(II)Maximum

10.0
(I)

emission probability corresponding to a total annihilation in the source per 100 disintegrations.

70-17
Radionuclide

Half-life

Lead-203 (203Pb)

(I)Mean

51.873 (9)
hours

Electron emission

Photon emission

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

Type

Energy (MeV)

Emission
probability
(per 100
disintegrations)

eA

0.055

3.0

ce

0.194

13.3

0.010
0.071-0.073
0.083

37.0
69.6
19.4

0.279
0.401

80.8
3.4

energy of the spectrum.

(II)Maximum

emission probability corresponding to a total annihilation in the source per 100 disintegrations.

70-18

Iodinated[125I] Albumin Injection


Iodinated[125I] Human Albumin Injection
Definition Iodinated[125I] Albumin Injection is a sterile solution of albumin that has been
iodinated with iodine-125 and subsequently freed from iodide[125I] ion, made isotonic with blood
by the addition of Sodium Chloride and containing a suitable antimicrobial preservative such as
Benzyl Alcohol. It is prepared from Albumin Solution and contains not less than 1% of protein.
Before addition of carrier albumin, if this is added, the albumin is uniformly iodinated to an extent
that does not exceed the equivalent of one atom of iodine for each molecule of albumin. The
content of iodine-125 activity is not less than 85.0% and not more than 115.0% of the content of
iodine-125 stated on the label at the date stated on the label.
The injection complies with the requirements stated under Radiopharmaceutical Preparations and with the
following requirements.
Characteristics A clear, colourless or faintly yellow solution.
Iodine-125 has a half-life of 60.1 days and emits gamma-radiation and X-rays.
Identification
A. The gamma-ray and X-ray spectrum, measured in a suitable instrument, does not differ
significantly from that of a standardised iodine-125 solution other than any differences attributable
to the presence of iodine-126. The most prominent gamma-photon of iodine-125 has an energy of
0.027 MeV (corresponding to the K X-ray of tellurium). The presence of iodine-126 is shown by
major gamma-photons of 0.388 and 0.666 MeV. Iodine-126 has a half-life of 13.0 days.
B. When examined in an ultracentrifuge, it has the sedimentation coefficient of normal human
albumin.
Acidity or alkalinity pH, 6.5 to 8.5, Appendix V L.
Radionuclidic purity Measure the gamma-ray and X-ray spectrum in a suitable instrument by
comparison with standardised solutions of iodine-125 and caesium-137. Determine the relative
amounts of iodine-125 and iodine-126 present on the assumption that the 0.666 MeV gammaphoton of iodine-126 is emitted in 33% of disintegrations and that the 0.66 MeV gamma-photon of
caesium-137 is emitted in 86% of disintegrations. Not more than 1.0% of the total activity is due to
iodine-126 at the date stated on the label.
Radiochemical purity Submit a volume containing not less than 0.5 mg of albumin to
electrophoresis on a strip of filter paper (30 cm 5 cm) at 500 volts for 1 hour in a solution
containing 5 g of barbitone sodium, 3.25 g of sodium acetate, 4 g of sodium octanoate and 34.2 ml of
0.1M hydrochloric acid in sufficient water to produce 100 ml. Allow the paper to dry and determine
the area of radioactivity using a suitable instrument. Not less than 95% of the activity on the paper
occurs in a position corresponding to that which would be occupied by treating normal human
albumin at the same time and in the same manner.
Protein
A. To 1 ml in a 75-ml boiling tube add 1 ml of saline solution and carry out the method for the determination of protein in blood products, Appendix VIII H, Method VI, beginning at the words add 2 ml
and ending at the words as indicator and taking care to absorb liberated iodine-125. Each
ml of 0.02M hydrochloric acid VS is equivalent to 1.75 mg of protein.
B. Carry out the test for Radiochemical purity using a volume containing 0.2 to 0.5 mg of albumin
but using a strip of cellulose acetate (30 cm 5 cm) in place of the paper. Dry the strip at about
80 to 100 for 15 minutes and stain for 15 minutes in a solution of 0.2 g of naphthalene black 12B in
a mixture of 10 ml of glacial acetic acid and 90 ml of methanol. Wash the strip in a mixture of 12 ml of
glacial acetic acid and 88 ml of methanol until the background is white and then wash for 10 minutes
in 1M acetic acid and finally in water. Dry the strip between blotting paper pressed between glass
plates. The distribution of the stained protein does not deviate significantly from that obtained by
treating normal human albumin at the same time and in the same manner.
Pyrogens Complies with the test for pyrogens, Appendix XIV D. Use per kg of the rabbits weight
either 0.1 ml or a quantity corresponding to 370 kBq at the date stated on the label, whichever is
the less.
Assay Determine the activity using suitable counting equipment by comparison with a standardised
iodine-125 solution or by measurement in an instrument calibrated with the aid of such a solution.
An instrument incorporating a scintillation detector, such as a thin sodium iodide crystal, should be
employed and the instrument should be set so that the contribution from iodine-126 is minimal.
Standardised iodine-125 solutions available from Amersham International plc, Amersham, HP7
9LL, England, are suitable.
Storage Iodinated[125I] Albumin Injection should be stored at a temperature of 2 to 8.
Labelling The label states the concentration of albumin.

70-19

Ammonia[13N] Injection
1/01
Ammonia[13N] Injection complies with the requirements of the 3rd edition of the European Pharmacopoeia
[1492]. These requirements are reproduced after the heading Definition below.
Action and use Radiodiagnostic.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Ammonia (13N) injection is a sterile solution of [13N]ammonia for diagnostic use. The injection
contains not less than 90.0 per cent and not more than 110.0 per cent of the declared nitrogen-13
radioactivity at the date and time stated on the label. Not less than 99 per cent of the total radioactivity corresponds to nitrogen-13 in the form of [13N]ammonia. Not less than 99.0 per cent of
the total radioactivity corresponds to nitrogen-13.
PRODUCTION
RADIONUCLIDE PRODUCTION
Nitrogen-13 is a radioactive isotope of nitrogen which may be produced by various nuclear
reactions, such as proton irradiation of carbon-13 or oxygen-16, or deuteron irradiation of
carbon-12.
RADIOCHEMICAL SYNTHESIS
[13N]Ammonia may be prepared by proton irradiation of water followed by the reduction of the
resulting [13N]nitrates/nitrites mixture with a reducing agent. The [13N]ammonia formed is distilled
from the reaction mixture and trapped in a slightly acidic solution.
Other methods may produce [13N]ammonia in-target by proton irradiation of water containing
a small amount of ethanol or acetic acid, or by proton irradiation of a slurry of [13C]carbon powder
in water. The resulting solution can be purified, to remove radionuclidic and radiochemical
impurities, using anion and cation exchange columns.
Production systems and their performance comply with the requirements prescribed in the
monograph on Radiopharmaceutical preparations (0125).
STARTING MATERIALS
Target materials comply with the requirements prescribed in the monograph on Radiopharmaceutical
preparations (0125).
CHARACTERS
A clear, colourless solution.
Nitrogen-13 has a half-life of 9.96 min and emits positrons with a maximum energy of 1.198 MeV,
followed by annihilation gamma radiation of 0.511 MeV.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The only gamma photons have an energy of 0.511 MeV
and, depending on the measurement geometry, a sum peak of 1.022 MeV may be observed.
B. It complies with test (a) for radionuclidic purity (see Tests).
C. Examine the chromatograms obtained in the test for radiochemical purity. The principal peak in
the radiochromatogram obtained with the test solution has approximately the same retention time
as the principal peak in the radiochromatogram obtained with the reference solution.
TESTS
pH (2.2.3). The pH of the injection is 5.5 to 8.5.
Chemical purity
Aluminium. In a test-tube about 12 mm in internal diameter, mix 1 ml of acetate buffer solution pH
4.6 R and 2 ml of a 1 in 20 dilution of the preparation to be examined in water R. Add 0.05 ml of a
10 g/l solution of chromazurol S R. After 3 min, the colour of the solution is not more intense than
that of a standard prepared at the same time and in the same manner using 2 ml of a 1 in 20 dilution
of aluminium standard solution (2 ppm Al) R (2 ppm).
The injection may be released for use before completion of the test.
Radionuclidic purity
(a) Half-life. The half-life as measured by methods described in the monograph on Radiopharmaceutical preparations (0125) is between 9 min and 11 min.

70-20
(b) Gamma emitting impurities. Retain a sample of the preparation to be examined for 2 h. Examine
the gamma-ray spectrum of the decayed material for the presence of radionuclidic impurities,
which should, where possible, be identified and quantified. The total gamma radioactivity due to
these impurities does not exceed 1.0 per cent of the total radioactivity.
The injection may be released for use before completion of tests (a) and (b).
Radiochemical purity Examine by liquid chromatography (2.2.29).
Test solution. The preparation to be examined.
Reference solution. Dilute 1.0 ml of dilute ammonia R2 to 10.0 ml with water R.
The chromatographic procedure may be carried out using:
a column 0.04 m long and 4.0 mm in internal diameter packed with cation exchange resin R
(10 m),
as mobile phase at a flow rate of 2 ml/min 0.002M nitric acid,
a suitable radioactivity detector,
a conductivity detector,
a loop injector,
maintaining the column at a constant temperature between 20C and 30C.
Inject separately the test solution and the reference solution. The chromatogram obtained with
the radioactivity detector and the test solution shows a principal peak with approximately the same
retention time as the peak in the chromatogram obtained with the reference solution and the
conductivity detector. Not less than 99 per cent of the total radioactivity corresponds to nitrogen13 in the form of ammonia.
The injection may be released for use before completion of the test.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Bacterial endotoxins (2.6.14). Not more than 175/V I.U. of endotoxin per millilitre, V being the
maximum recommended dose in millilitres. The injection may be released for use before
completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations
(0125) using suitable equipment by comparison with a standardised fluorine-18 solution or by using
an instrument calibrated with the aid of such a solution. Standardised fluorine-18 solutions are
available from laboratories recognised by the competent authority.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
IMPURITIES
A. [13N]O2,
B. [13N]O3,
C. [18F],
D. H2[15O].
__________________________________________________________________________________________________________ Ph Eur

70-21

Chromium[51Cr] Edetate Injection


Chromium[51Cr] Edetate Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0266]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Chromium (51Cr) edetate injection is a sterile solution containing chromium-51 in the form of a
complex of chromium(III) with ethylenediaminetetra-acetic acid, the latter being present in excess.
It may be made isotonic by the addition of sodium chloride and may contain a suitable antimicrobial
preservative such as benzyl alcohol. Chromium-51 is a radioactive isotope of chromium and may be
prepared by the neutron irradiation of chromium, either of natural isotopic composition or
enriched in chromium-50. The injection contains not less than 90.0 per cent and not more than
110.0 per cent of the declared chromium-51 radioactivity at the date and hour stated on the label.
Not less than 95 per cent of the radioactivity corresponds to chromium-51 in the form of chromium
edetate. The injection contains a variable quantity of chromium (Cr) not exceeding 1 mg per
millilitre.
CHARACTERS
A clear, violet solution.
Chromium-51 has a half-life of 27.7 days and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised chromium-51 solution. Standardised chromium-51 solutions are available from
laboratories recognised by the competent authority. The gamma photon has an energy of
0.320 MeV.
B. Examine the electrophoretogram obtained in the test for radiochemical purity. The distribution
of radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 3.5 to 6.5.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ
significantly from that of a standardised chromium-51 solution.
Radiochemical purity Examine by zone electrophoresis (2.2.31), using a paper strip as the
support and a solution containing 0.2 g/l of barbital sodium R and 10 g/l of sodium nitrate R as the
electrolyte solution. A paper with the following characteristics is suitable: mass per unit area
120 g/m2; thickness 0.22 mm; capillary rise 105 mm to 115 mm per 30 min.
Apply to the paper 10 l of the injection as a 3 mm band at a position 10 cm from the cathode.
Apply an electric field of about 30 V per centimetre for 30 min using a stabilised current.
[51Cr]chromium edetate moves about 5 cm towards the anode. [51Cr]Chromate moves about
10 cm towards the anode and [51Cr] chromic ion moves about 7 cm towards the cathode.
Determine the distribution of the radioactivity using a suitable detector. Not less than 95 per cent
of the total radioactivity is found in the band corresponding to [51Cr]chromium edetate.
Chromium Prepare a reference solution (1 mg per millilitre of Cr) as follows: dissolve 0.96 g of
chromic potassium sulphate R and 2.87 g of sodium edetate R in 50 ml of water R, boil for 10 min, cool,
adjust to pH 3.5 to 6.5 using dilute sodium hydroxide solution R and dilute to 100.0 ml with water R.
Measure the absorbance (2.2.25) of the injection to be examined and the reference solution at the
absorption maximum at 560 nm. The absorbance of the injection to be examined is not greater than
that of the reference solution.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable equipment by comparison with a standardised chromium-51 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-22

Cyanocobalamin[57Co] Capsules
Cyanocobalamin[57Co] Capsules comply with the requirements of the 3rd edition of the European
Pharmacopoeia [0710]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Cyanocobalamin (57Co) capsules contain [57Co]-a-(5,6-dimethylbenzimidazol-1-yl)cobamide
cyanide and may contain suitable auxiliary substances. Cobalt-57 is a radioactive isotope of cobalt
and may be produced by proton irradiation of nickel. Cyanocobalamin (57Co) may be prepared by
the growth of suitable micro-organisms on a medium containing (57Co) cobaltous ion. Not less than
90 per cent of the cobalt-57 is in the form of cyanocobalamin. The capsules comply with the
requirements for hard capsules in the monograph on Capsules (0016), unless otherwise justified and
authorised.
CHARACTERS
Hard gelatin capsules.
Cobalt-57 has a half-life of 271 days and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised cobalt-57 solution. Standardised cobalt-57 and cobalt-58 solutions are available from
laboratories recognised by the competent authority. The most prominent gamma photon of cobalt57 has an energy of 0.122 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The principal peak in
the radiochromatogram obtained with the test solution has a retention time similar to that of the
peak in the chromatogram obtained with the reference solution.
TESTS
Radionuclidic purity Record the gamma-ray spectrum as described in the monograph on Radiopharmaceutical preparations (0125) using a suitable instrument calibrated with the aid of standardised
cobalt-57 and cobalt-58 solutions. The spectrum does not differ significantly from that of the
standardised cobalt-57 solution. Determine the relative amounts of cobalt-57, cobalt-56 and
cobalt-58 present. Cobalt-56 has a half-life of 78 days and its presence is shown by gamma photons
of energy 0.847 MeV. Cobalt-58 has a half-life of 70.8 days and its presence is shown by gamma
photons of energy 0.811 MeV. Not more than 0.1 per cent of the total radioactivity is due to
cobalt-56, cobalt-58 and other radionuclidic impurities.
Radiochemical purity Examine by liquid chromatography (2.2.29).
Test solution. Dissolve the contents of a capsule in 1.0 ml of water R and allow to stand for 10 min.
Centrifuge at 2000 r/min for 10 min. Use the supernatant.
Reference solution. Dissolve 10 mg of cyanocobalamin CRS in the mobile phase and dilute to 100 ml
with the mobile phase. Dilute 2 ml of the solution to 100 ml with the mobile phase. Use within 1 h.
The chromatographic procedure may be carried out using:
a stainless steel column 0.25 m long and 4 mm in internal diameter packed with octylsilyl silica
gel for chromatography R (5 m),
as mobile phase at a flow rate of 1.0 ml per minute a mixture prepared as follows: mix 26.5
volumes of methanol R and 73.5 volumes of a 10 g/l solution of disodium hydrogen phosphate R,
adjust to pH 3.5 using phosphoric acid R and use within 2 days,
a radioactivity detector adjusted for cobalt-57,
as detector a spectrophotometer set at 361 nm,
a loop injector.
Inject 100 l of the test solution and record the chromatogram for three times the retention time
of cyanocobalamin. Determine the peak areas and calculate the percentage of cobalt-57 present as
cyanocobalamin. Inject 100 l of the reference solution and record the chromatogram for 30 min.
Disintegration The capsules comply with the test for disintegration of tablets and capsules (2.9.1)
except that one capsule is used in the test instead of six.
Uniformity of content Determine by measurement in a suitable counting assembly and under
identical geometrical conditions the radioactivity of each of not less than ten capsules. Calculate the
average radioactivity per capsule. The radioactivity of no capsule differs by more than 10 per cent

70-23
from the average. The relative standard deviation is less than 3.5 per cent.
RADIOACTIVITY
The average radioactivity determined in the test for uniformity of content is not less than 90.0 per
cent and not more than 110.0 per cent of the declared cobalt-57 radioactivity, at the date stated on
the label.
STORAGE
Store in an airtight container, protected from light, at a temperature of 2C to 8C, in the
conditions prescribed in the monograph on Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-24

Cyanocobalamin[58Co] Capsules
1/01
Cyanocobalamin[58Co] Capsules comply with the requirements of the 3rd edition of the European
Pharmacopoeia [1505]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Cyanocobalamin (58Co) capsules contain [58Co]-a-(5,6-dimethylbenzimidazol-1-yl)cobamide
cyanide and may contain suitable auxiliary substances. Cobalt-58 is a radioactive isotope of cobalt
and may be produced by neutron irradiation of nickel. Cyanocobalamin (58Co) may be prepared by
the growth of suitable micro-organisms on a medium containing (58Co) cobaltous ion. Not less than
84 per cent of the cobalt-58 is in the form of cyanocobalamin. The capsules comply with the
requirements for hard capsules in the monograph on Capsules (0016), unless otherwise justified and
authorised. The average radioactivity is not less than 90.0 per cent and not more than 110.0 per
cent of the declared cobalt-58 radioactivity at the date stated on the label.
CHARACTERS
Hard gelatin capsules.
Cobalt-58 has a half-life of 70.9 days and emits beta (b+) radiation and gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised cobalt-58 solution. Standardised cobalt-58 solutions are available from laboratories
recognised by the competent authority. The most prominent gamma photons of cobalt-58 have
energies of 0.511 MeV (annihilation radiation) and 0.811 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The principal peak in
the radiochromatogram obtained with the test solution has a retention time similar to that of the
peak in the chromatogram obtained with the reference solution.
TESTS
Radionuclidic purity Record the gamma-ray spectrum as described in the monograph on Radiopharmaceutical preparations (0125) using a suitable instrument calibrated with the aid of standardised
cobalt-58, cobalt-57 and cobalt-60 solutions. The spectrum does not differ significantly from that
of the standardised cobalt-58 solution. Standardised cobalt-58, cobalt-57 and cobalt-60 solutions
are available from laboratories recognised by the competent authority. Determine the relative
amounts of cobalt-58, cobalt-57 and cobalt-60 present. Cobalt-57 has a half-life of 272 days and its
presence is shown by gamma photons of energy 0.122 MeV. Cobalt-60 has a half-life of 5.27 years
and its presence is shown by gamma photons of energies 1.173 MeV and 1.333 MeV. Not more
than 1 per cent of the total radioactivity is due to cobalt-60 and not more than 2 per cent of the
total radioactivity is due to cobalt-57, cobalt-60 and other radionuclidic impurities.
Radiochemical purity Examine by liquid chromatography (2.2.29).
Test solution. Dissolve the contents of a capsule in 1.0 ml of water R and allow to stand for 10 min.
Centrifuge at 2000 r/min for 10 min. Use the supernatant.
Reference solution. Dissolve 10 mg of cyanocobalamin CRS in the mobile phase and dilute to 100 ml
with the mobile phase. Dilute 2 ml of the solution to 100 ml with the mobile phase. Use within 1 h
of preparation.
The chromatographic procedure may be carried out using:
a stainless steel column 0.25 m long and 4 mm in internal diameter packed with octylsilyl silica
gel for chromatography R (5 m),
as mobile phase at a flow rate of 1.0 ml/min a mixture prepared as follows: mix 26.5 volumes of
methanol R and 73.5 volumes of a 10 g/l solution of disodium hydrogen phosphate R, adjusted to
pH 3.5 with phosphoric acid R and use within 2 days,
a radioactivity detector adjusted for cobalt-58,
as detector a spectrophotometer set at 361 nm,
a loop injector.
Inject 100 l of the test solution and record the chromatogram for three times the retention time
of cyanocobalamin. Determine the peak areas and calculate the percentage of cobalt-58 present as
cyanocobalamin. Inject 100 l of the reference solution and record the chromatogram for 30 min.
Disintegration The capsules comply with the test for disintegration of tablets and capsules (2.9.1)
except that one capsule is used in the test instead of six.

70-25
Uniformity of content Determine by measurement in a suitable counting assembly and under
identical geometrical conditions the radioactivity of each of not less than ten capsules. Calculate the
average radioactivity per capsule. The radioactivity of no capsule differs by more than 10 per cent
from the average. The relative standard deviation is less than 3.5 per cent.
RADIOACTIVITY
The average radioactivity determined in the test for uniformity of content is not less than 90.0 per
cent and not more than 110.0 per cent of the declared cobalt-58 radioactivity, at the date stated on
the label.
STORAGE
Store in an airtight container, protected from light, at a temperature of 2C to 8C, in the
conditions prescribed in the monograph on Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-26

Cyanocobalamin[57Co] Solution
Cyanocobalamin[57Co] Solution complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0269]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Cyanocobalamin (57Co) solution is a solution of [57Co]-a-(5,6-dimethylbenzimidazol-1-yl)cobamide
cyanide and may contain a stabiliser and an antimicrobial preservative. Cobalt-57 is a radioactive
isotope of cobalt and may be produced by the irradiation of nickel with protons of suitable energy.
Cyanocobalamin (57Co) may be prepared by the growth of suitable micro-organisms on a medium
containing (57Co) cobaltous ion. The solution contains not less than 90.0 per cent and not more
than 110.0 per cent of the declared cobalt-57 radioactivity at the date stated on the label. Not less
than 90 per cent of the cobalt-57 is in the form of cyanocobalamin.
CHARACTERS
A clear, colourless or slightly pink solution. Cobalt-57 has a half-life of 271 days and emits gamma
radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised cobalt-57 solution. Standardised cobalt-57 and cobalt-58 solutions are available from
laboratories recognised by the competent authority. The most prominent gamma photon of cobalt57 has an energy of 0.122 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The principal peak in
the radiochromatogram obtained with the solution to be examined has a retention time similar to
that of the peak in the chromatogram obtained with the reference solution.
TESTS
pH (2.2.3). The pH of the solution is 4.0 to 6.0.
Radionuclidic purity Record the gamma-ray spectrum as described in the monograph on Radiopharmaceutical preparations (0125) using a suitable instrument calibrated with the aid of standardised
cobalt-57 and cobalt-58 solutions. The spectrum does not differ significantly from that of the
standardised cobalt-57 solution. Determine the relative amounts of cobalt-57, cobalt-56 and
cobalt-58 present. Cobalt-56 has a half-life of 78 days and its presence is shown by gamma photons
of energy 0.847 MeV. Cobalt-58 has a half-life of 70.8 days and its presence is shown by gamma
photons of energy 0.811 MeV. Not more than 0.1 per cent of the total radioactivity is due to
cobalt-56, cobalt-58 and other radionuclidic impurities.
Radiochemical purity Examine by liquid chromatography (2.2.29).
Reference solution. Dissolve 10 mg of cyanocobalamin CRS in the mobile phase and dilute to 100 ml
with the mobile phase. Dilute 2 ml of the solution to 100 ml with the mobile phase. Use within 1 h.
The chromatographic procedure may be carried out using:
a stainless steel column 0.25 m long and 4 mm in internal diameter packed with octylsilyl silica
gel for chromatography R (5 m),
as mobile phase at a flow rate of 1.0 ml per minute a mixture prepared as follows: mix 26.5
volumes of methanol R and 73.5 volumes of a 10 g/l solution of disodium hydrogen phosphate R,
adjust to pH 3.5 using phosphoric acid R and use within 2 days,
a radioactivity detector adjusted for cobalt-57,
as detector a spectrophotometer set at 361 nm,
a loop injector.
Inject 100 l of the solution to be examined and record the chromatogram for three times the
retention time of cyanocobalamin. Determine the peak areas and calculate the percentage of
cobalt-57 present as cyanocobalamin. Inject 100 l of the reference solution and record the
chromatogram for 30 min.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised cobalt-57 solution.
STORAGE
Store protected from light at a temperature of 2C to 8C under the conditions prescribed in the
monograph on Radiopharmaceutical preparations (0125).

70-27
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-28

Cyanocobalamin[58Co] Solution
Cyanocobalamin[58Co] Solution complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0270]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Cyanocobalamin (58Co) solution is a solution of [58Co]-a-(5,6-dimethylbenzimidazol-1-yl)cobamide
cyanide and may contain a stabiliser and an antimicrobial preservative. Cobalt-58 is a radioactive
isotope of cobalt and may be produced by neutron irradiation of nickel. Cyanocobalamin (58Co)
may be prepared by the growth of suitable micro-organisms on a medium containing (58Co) cobaltous ion. The solution contains not less than 90.0 per cent and not more than 110.0 per cent of the
declared cobalt-58 radioactivity at the date stated on the label. Not less than 90 per cent of the
cobalt-58 is in the form of cyanocobalamin.
CHARACTERS
A clear, colourless or slightly pink solution.
Cobalt-58 has a half-life of 70.8 days and emits beta (b+) radiation and gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised cobalt-58 solution. Standardised cobalt-58, cobalt-57 and cobalt-60 solutions are
available from laboratories recognised by the competent authority. The most prominent gamma
photons of cobalt-58 have energies of 0.511 MeV (annihilation radiation) and 0.811 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The principal peak in
the radiochromatogram obtained with the solution to be examined has a retention time similar to
that of the peak in the chromatogram obtained with the reference solution.
TESTS
pH (2.2.3). The pH of the solution is 4.0 to 6.0.
Radionuclidic purity Record the gamma-ray spectrum as described in the monograph on Radiopharmaceutical preparations (0125) using a suitable instrument having adequate resolution and
calibrated with the aid of standardised cobalt-58, cobalt-57 and cobalt-60 solutions. The spectrum
does not differ significantly from that of the standardised cobalt-58 solution. Determine the relative
amounts of cobalt-58, cobalt-57 and cobalt-60 present. Cobalt-57 has a half-life of 271 days and its
presence is shown by gamma photons of energy 0.122 MeV. Cobalt-60 has a half-life of 5.27 years
and its presence is shown by gamma photons of energies 1.173 MeV and 1.332 MeV. Not more
than 1 per cent of the total radioactivity is due to cobalt-60 and not more than 2 per cent of the
total radioactivity is due to cobalt-57, cobalt-60 and other radionuclidic impurities.
Radiochemical purity Examine by liquid chromatography (2.2.29).
Reference solution. Dissolve 10 mg of cyanocobalamin CRS in the mobile phase and dilute to 100 ml
with the mobile phase. Dilute 2 ml of the solution to 100 ml with the mobile phase. Use within 1 h.
The chromatographic procedure may be carried out using:
a stainless steel column 0.25 m long and 4 mm in internal diameter packed with octylsilyl silica
gel for chromatography R (5 m),
as mobile phase at a flow rate of 1.0 ml per minute a mixture prepared as follows: mix 26.5
volumes of methanol R and 73.5 volumes of a 10 g/l solution of disodium hydrogen phosphate R,
adjust to pH 3.5 using phosphoric acid R and use within 2 days,
a radioactivity detector adjusted for cobalt-58,
as detector a spectrophotometer set at 361 nm,
a loop injector.
Inject 100 l of the solution to be examined and record the chromatogram for three times the
retention time of cyanocobalamin. Determine the peak areas and calculate the percentage of
cobalt-58 present as cyanocobalamin. Inject 100 l of the reference solution and record the
chromatogram for 30 min.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised cobalt-58 solution or by
measurement in an instrument calibrated with the aid of such a solution.

70-29
STORAGE
Store protected from light at a temperature of 2C to 8C under the conditions prescribed in the
monograph on Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-30

Fludeoxyglucose[18F] Injection
CH2OH
O
OH

OH

HO
[18F]
Fludeoxyglucose[18F] Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [1325]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Fludeoxyglucose (18F) injection is a sterile solution of 2-[18F]fluoro-2-deoxy-D-glucopyranose
(2-[18F]fluoro-2-deoxy-D-glucose) for diagnostic use. The injection contains not less than 90.0 per
cent and not more than 110.0 per cent of the declared fluorine-18 radioactivity at the date and
time stated on the label. Not less than 95 per cent of the radioactivity corresponds to fluorine-18 in
the form of 2-[18F]fluoro-2-deoxy-D-glucose and 2-[18F]fluoro-2-deoxy-D-mannose, with the
2-[18F]fluoro-2-deoxy-D-mannose fraction not exceeding 10 per cent of the total radioactivity. Not
less than 99.0 per cent of the radioactivity corresponds to fluorine-18. The content of 2-fluoro-2deoxy-D-glucose is not more than 10 mg per maximum recommended dose of injection.
PRODUCTION
RADIONUCLIDE PRODUCTION
Fluorine-18 is a radioactive isotope of fluorine which may be produced by various nuclear
reactions induced by proton irradiation of oxygen-18, deuteron irradiation of neon-20, helium-3 or
helium-4 irradiation of oxygen-16.
RADIOCHEMICAL SYNTHESIS
2-[18F]Fluoro-2-deoxy-D-glucose may be prepared by various chemical synthetic pathways, which
lead to different products in terms of specific radioactivity, by-products and possible impurities.
Most widely used is the method of phase transfer catalysed nucleophilic substitution of 1,3,4,6tetra-O-acetyl-2-O-trifluoromethanesulphonyl-b-D-mannopyranose with [18F]fluoride. Generally,
[18F]fluoride is adsorbed on an anion-exchange resin and eluted with a solution of potassium
carbonate which is then evaporated to dryness. Addition of a phase transfer catalyst such as an
aminopolyether in dry acetonitrile may be used to enhance the nucleophilicity of the [18F]fluoride
so that it reacts easily with the tetra-acetylated mannosyltriflate at elevated temperature. Hydrolysis
under either alkaline or acidic conditions yields 2-[18F]fluoro-2-deoxy-D-glucose. Hydrolysis using
hydrochloric acid may lead to the formation of 2-chloro-2-deoxy-D-glucose. Hydrolysis under
alkaline conditions may lead to the formation of 2-[18F]fluoro-2-deoxy-D-mannose as a by-product.
Variations of the method substitute the aminopolyether by a tetra-alkyl ammonium salt, or use
solid phase catalysed nucleophilic substitution on derivatised anion-exchange resin, e.g. derivatised
with 4-(4-methylpiperidino)pyridine.
Electrophilic pathways for production of 2-[18F]fluoro-2-deoxy-D-glucose proceed by the
reaction of molecular [18F]fluorine or [18F]acetylhypofluorite with 3,4,6-tri-O-acetyl-D-glucal.
[18F]Acetylhypofluorite is obtained by conversion of molecular [18F]fluorine on a solid complex of
acetic acid and potassium acetate. The production of molecular [18F]fluorine requires the addition
of small amounts of fluorine to the neon target gas, usually from 0.1 per cent to 1 per cent,
resulting in the reduction of the specific radioactivity of the end-product. Hydrolysis of the
O-acetyl protected [18F]fluorinated sugar yields 2-[18F]fluoro-2-deoxy-D-glucose and usually small
amounts of 2-[18F]fluoro-2-deoxy-D-mannose.
The preparation can be purified by serial chromatography on combinations of ion-retardation
resin, ion-exchange resin, alumina and octadecyl derivatised silica gel. Removal of the phase
transfer catalyst can be achieved by different methods, all using combinations of separation
cartridges.
Production systems and their performance comply with the requirements set by the competent
authority.
STARTING MATERIALS
1. Target materials

70-31
Each batch of target material must be tested in special production runs before its use in routine
fluorine-18 production and manufacture of the preparation, to ensure that under specified
conditions, the target yields fluorine-18 in the desired quantity and quality.
2. Precursors for organic synthesis
It is recommended to test the precursors in production runs before their use for the manufacture
of the preparation, to ensure that under specified production conditions, the precursors yield the
preparation in the desired quantity and quality.
1,3,4,6-Tetra-O-acetyl-2-O-trifluoromethanesulphonyl-b-D-mannopyranose Examine by
infrared absorption spectrophotometry (2.2.24), comparing with the Ph. Eur. reference spectrum of
1,3,4,6-tetra-O-acetyl-2-O-trifluoromethane-sulphonyl-b-D-mannopyranose.
Melting point (2.2.14): 119C to 122C.
3,4,6-Tri-O-acetyl-D-glucal Examine by infrared absorption spectrophotometry (2.2.24),
comparing with the Ph. Eur. reference spectrum of 3,4,6-tri-O-acetyl-D-glucal.
Melting point (2.2.14): 53C to 55C.
CHARACTERS
A clear, colourless or slightly yellow solution.
Fluorine-18 has a half-life of 109.8 min and emits positrons with a maximum energy of
0.633 MeV, followed by annihilation gamma radiation of 0.511 MeV.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The only gamma photons have an energy of 0.511 MeV;
and depending on the measurement geometry, a sum peak of 1.022 MeV may be observed.
B. It complies with the test for radionuclidic purity (see Tests).
C. Examine the chromatograms obtained in test (a) for radiochemical purity. The principal peak in
the radio-chromatogram obtained with the test solution has approximately the same retention time
as the principal peak in the chromatogram obtained with reference solution (b).
TESTS
pH (2.2.3). The pH of the injection is 4.5 to 8.5.
Chemical purity Particular tests for chemical purity may be omitted if the substances mentioned are not
used or cannot be formed in the production process.
(a) 2-Fluoro-2-deoxy-D-glucose and 2-chloro-2-deoxy-D-glucose Examine by liquid chromatography (2.2.29).
Test solution. The preparation to be examined.
Reference solution (a). Dissolve 10 mg of glucose R in water R and dilute to 100 ml with the same
solvent.
Reference solution (b). Dissolve 10 mg of 2-fluoro-2-deoxy-D-glucose R in water R and dilute to V with the
same solvent, V being the maximum recommended dose in millilitres.
Reference solution (c). Dissolve 1.0 mg of 2-chloro-2-deoxy-D-glucose CRS in water R and dilute to 2.0 ml
with the same solvent. Dilute 1 ml of this solution to V with the same solvent, V being the maximum
recommended dose in millilitres.
The chromatographic procedure may be carried out using:
a column 0.25 m long and 4.0 mm in internal diameter packed with strongly basic anion-exchange
resin for chromatography R (10 m),
as mobile phase at a flow rate of 1 ml/min 0.1M sodium hydroxide protected against
contamination by carbon dioxide,
a suitable radioactivity detector for radiochemical purity testing,
a detector suitable for carbohydrates in the required concentration range,
a loop injector,
maintaining the column at a constant temperature between 20C and 30C.
Equilibrate the column with the mobile phase until a stable baseline is achieved.
Inject separately reference solutions (a), (b) and (c). If the validation studies exclude the
formation of 2-chloro-2-deoxy-D-glucose inject separately reference solutions (a) and (b).
Continue the chromatography for twice the retention time of D-glucose, 2-fluoro-2-deoxy-Dglucose and when required, 2-chloro-2-deoxy-D-glucose respectively.
Inject the test solution. The chromatogram obtained with the detector for carbohydrates shows
a principal peak corresponding to D-glucose (test solutions from nucleophilic pathways) or 2fluoro-2-deoxy-D-glucose (test solutions from electrophilic pathways). When the chromatograms
are recorded in the prescribed conditions, 2-chloro-2-deoxy-D-glucose elutes after 2-fluoro-2deoxy-D-glucose, but their corresponding peaks may not be completely resolved. In the chromatogram obtained with the test solution, the areas of the peaks corresponding to 2-fluoro-2-deoxy-D-

70-32
glucose and 2-chloro-2-deoxy-D-glucose are not greater than the areas of the peaks in the chromatograms obtained with reference solution (b) and/or reference solution (c) (10 mg of 2-fluoro-2deoxy-D-glucose per V and 0.5 mg of 2-chloro-2-deoxy-D-glucose per V respectively).
(b) Aminopolyether This test is performed only on the bulk solution before addition of sodium chloride by the
producer and it is not intended for the final preparation to be injected. Examine by thin-layer chromatography (2.2.27), using a TLC silica gel plate R.
Test solution. The preparation to be examined.
Reference solution. Dissolve 0.110 g of aminopolyether R in water R and dilute to 10.0 ml with the same
solvent. Dilute 0.2 ml of this solution to V with the same solvent, V being the maximum
recommended dose in millilitres.
Apply separately to the plate 2 l of the test solution and 2 l of the reference solution. Develop
over a path of about 8 cm using a mixture of 1 volume of ammonia R and 9 volumes of methanol R.
Allow the plate to dry in air for 15 min. Expose the plate to iodine vapour for at least 10 min. In the
chromatogram obtained with the test solution the spot corresponding to aminopolyether is not
more intense than the spot in the chromatogram obtained with the reference solution (2.2 mg
per V).
(c) Tetra-alkyl ammonium salts Examine by liquid chromatography (2.2.29).
Test solution. The preparation to be examined.
Reference solution. Dilute 2.1 ml of 0.1M tetrabutylammonium hydroxide to 20 ml with water R. Dilute
1 ml of this solution to V with the same solvent, V being the maximum recommended dose in
millilitres.
The chromatographic procedure may be carried out using:
a column 0.125 m long and 4.0 mm in internal diameter packed with octadecylsilyl silica gel for
chromatography R (5 m),
as mobile phase at a flow rate of 0.6 ml/min a mixture of 25 volumes of a 0.95 g/l solution of
toluenesulphonic acid R and 75 volumes of acetonitrile R,
as detector a spectrophotometer set at 254 nm,
a loop injector,
maintaining the column at a constant temperature between 20C and 30C.
Equilibrate the column with the mobile phase until a stable baseline is obtained.
Inject the reference solution. Continue the chromatography for twice the retention time of
tetrabutylammonium ions.
Inject the test solution. In the chromatogram obtained with the test solution, the area of the peak
corresponding to tetrabutylammonium ions is not greater than the area of the peak in the chromatogram obtained with the reference solution (2.75 mg per V).
(d) Solid phase derivatisation agent 4-(4-methylpiperidino)pyridine Examine by ultraviolet
spectrophotometry (2.2.25).
Test solution. The preparation to be examined.
Reference solution. Dissolve 20 mg of 4-(4-methylpiperidino)pyridine R in water R and dilute to 100.0 ml
with the same solvent. Dilute 0.1 ml of this solution to V with the same solvent, V being the
maximum recommended dose in millilitres.
Measure the absorbance of the test solution and the reference solution at the maximum of
263 nm. The absorbance of the test solution is not greater than that of the reference solution
(0.02 mg per V).
(e) Residual solvents (2.4.24). The concentration of acetonitrile does not exceed 4.1 mg per V, V
being the maximum recommended dose in millilitres. The injection may be released for use before
completion of the test.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). The half-life as measured by methods
described in the monograph on Radiopharmaceutical preparations (0125) is between 105 min and
115 min. The injection may be released for use before completion of the test.
Radiochemical purity
(a) Examine by liquid chromatography (2.2.29) as described in test (a) for chemical purity.
When the chromatograms obtained with the radioactivity detector are recorded in the prescribed
conditions, the principal peak in the chromatogram obtained with the test solution has the same
retention time as the peak obtained with reference solution (b) using the carbohydrate detector.
The retention times of 2-[18F]fluoro-2-deoxy-D-mannose and [18F]fluoride are approximately
90 per cent and approximately 50 per cent of that of 2-[18F]fluoro-2-deoxy-D-glucose respectively.
Other peaks in the chromatogram may be due to partially acetylated 2-[18F]fluoro-2-deoxy-Dglucose derivatives.
Calculate the percentage content of [18F] fluorinated substances from the areas of the peaks in
the chromatogram obtained with the test solution. The sum of the percentages of radioactivity
corresponding to 2-[18F]fluoro-2-deoxy-D-glucose and 2-[18F]fluoro-2-deoxy-D-mannose is not less

70-33
than 95 per cent of the total radioactivity with the 2-[18F]fluoro-2-deoxy-D-mannose fraction not
exceeding 10 per cent of the total radioactivity.
The method may underestimate or miss unhydrolysed or partially hydrolysed 2-[18F]fluoro-2deoxytetraacetyl-D-glucose, since these intermediate reaction products may further hydrolyse to
the desired end-product under the chromatographic conditions.
(b) Examine by thin-layer chromatography (2.2.27) as described in the monograph on Radiopharmaceutical preparations (0125) using a TLC silica gel plate R.
Test solution. The preparation to be examined.
Apply 2 l to 10 l to the plate. Develop over a path of 8 cm using a mixture of 5 volumes of
water R and 95 volumes of acetonitrile R. Allow the plate to dry in air for 15 min. Determine the
distribution of radioactivity using a suitable detector. Not less than 95 per cent of the total radioactivity is found in the spot corresponding to 2-fluoro-2-deoxy-D-glucose (Rf about 0.45).
Possible contaminants are [18F]fluoride (Rf 0.0); partially acetylated 2-[18F]fluoro-2-deoxy-Dglucose derivatives (Rf about 0.8-0.95).
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Bacterial endotoxins (2.6.14). Not more than 175/V I.U. of endotoxin per millilitre, V being the
maximum recommended dose in millilitres. The injection may be released for use before
completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations
(0125) using suitable counting equipment by comparison with a standardised fluorine-18 solution
or using an instrument calibrated with the aid of such a solution. Standardised fluorine-18 solutions
are available from laboratories recognised by the competent authority.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125). The accompanying information specifies the particular
synthetic pathway of production. The label on the actual container states the maximum
recommended dose in millilitres.
__________________________________________________________________________________________________________ Ph Eur

70-34

Gallium[67Ga] Citrate Injection


Gallium[67Ga] Citrate Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0555]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Gallium(67Ga) citrate injection is a sterile solution of gallium-67 in the form of gallium citrate. It
may be made isotonic by the addition of sodium chloride and sodium citrate and may contain a
suitable antimicrobial preservative such as benzyl alcohol. Gallium-67 is a radioactive isotope of
gallium and may be obtained by the irradiation, with protons of suitable energy, of zinc which may
be enriched in zinc-68. Gallium-67 may be separated from zinc by solvent extraction or column
chromatography. The injection contains not less than 90.0 per cent and not more than 110.0 per
cent of the declared gallium-67 radioactivity at the date and hour stated on the label. Not more
than 0.2 per cent of the total radioactivity is due to gallium-66.
CHARACTERS
A clear, colourless solution.
Gallium-67 has a half-life of 3.26 days and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised gallium-67 solution when measured either by direct comparison or by use of an
instrument calibrated with the aid of such a solution. Standardised gallium-67 solutions are
available from laboratories recognised by the competent authority. The most prominent gamma
photons have energies of 0.093 MeV, 0.185 MeV and 0.300 MeV.
B. To 0.2 ml of the injection to be examined add 0.2 ml of a solution containing 1 g/l of ferric
chloride R and 0.1 per cent V/V of hydrochloric acid R and mix. Compare the colour with that of a
solution containing 9 g/l of benzyl alcohol R and 7 g/l of sodium chloride R treated in the same manner.
A yellow colour develops in the test solution only.
TESTS
pH (2.2.3). The pH of the injection is 5.0 to 8.0.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ
significantly from that of a standardised gallium-67 solution, apart from any differences attributable
to the presence of gallium-66. Gallium-66 has a half-life of 9.4 h and its most prominent gamma
photon has an energy of 1.039 MeV. Not more than 0.2 per cent of the total radioactivity is due to
gallium-66.
Zinc To 0.1 ml of the injection to be examined add 0.9 ml of water R, 5 ml of acetate buffer solution
pH 4.7 R, 1 ml of a 250 g/l solution of sodium thiosulphate R and 5.0 ml of a dithizone solution
prepared as follows: dissolve 10 mg of dithizone R in 100 ml of methyl ethyl ketone R allow to stand
for 5 min, filter and immediately before use dilute the solution to ten times its volume with methyl
ethyl ketone R. Shake vigorously for 2 min and separate the organic layer. Measure the absorbance
(2.2.25) of the organic layer at 530 nm, using the organic layer of a blank solution as the
compensation liquid. The absorbance is not greater than that of the organic layer obtained with
0.1 ml of zinc standard solution (5 ppm Zn) R treated in the same manner.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised gallium-67 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-35

Indium[111In] Chloride Solution


Indium[111In] Chloride Solution complies with the requirements of the 3rd edition of the European
Pharmacopoeia [1227]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Indium(111In) chloride solution is a sterile solution of indium-111 as the chloride in aqueous hydrochloric acid containing no additives. Indium-111 is a radioactive isotope of indium and may be
produced by the irradiation of cadmium with protons of suitable energy. The solution contains not
less than 90.0 per cent and not more than 110.0 per cent of the declared indium-111 radioactivity
at the date and hour stated on the label. Not more than 0.25 per cent of the total radioactivity is
due to radionuclides other than indium-111. Not less than 95 per cent of the radioactivity corresponds to indium-111 in the form of ionic indium(III). The method of preparation is such that no
carrier is added and the specific radioactivity is not less than 1.85 GBq of indium-111 per
microgram of indium.
CHARACTERS
A clear, colourless solution.
Indium-111 has a half-life of 2.8 days and emits gamma radiation and X-rays.
IDENTIFICATION
A. Carry out the test after allowing sufficient time for short-lived impurities such as indium-110m to
decay. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised indium-111 solution apart from any differences due to the presence of
indium-114m, when measured either by direct comparison or by using an instrument calibrated
with the aid of such a solution. Standardised indium-111 and indium-114m solutions are available
from laboratories recognised by the competent authority. The most prominent gamma photons of
indium-111 have energies of 0.171 MeV and 0.245 MeV.
B. To 100 ml of silver nitrate solution R2 add 50 ml of the solution. A white precipitate is formed.
C. It complies with the test for pH (see Tests).
D. Examine the chromatogram obtained in the test for radiochemical purity. The principal peak
has an Rf value of 0.5 to 0.8.
TESTS
pH (2.2.3). The pH of the solution is 1.0 to 2.0.
Radionuclidic purity Record the gamma-ray and X-ray spectrum using a suitable instrument as
described in the monograph on Radiopharmaceutical preparations (0125). The spectrum does not
differ significantly from that of a standardised solution of indium-111 apart from any differences
due to the presence of indium-114m.
Indium-114m Carry out the test after allowing sufficient time for short-lived impurities such as indium-110m
to decay. Take a volume equivalent to 30 MBq and record the gamma-ray spectrum using a suitable
detector with a shield of lead, 6 mm thick, placed between the sample and the detector. The
response in the region corresponding to the 0.558 MeV photon and the 0.725 MeV photon of
indium-114m does not exceed that obtained using 75 kBq of a standardised solution of indium114m (0.25 per cent) measured under the same conditions, when all measurements are calculated
with reference to the date and hour of administration. Standardised indium-111 and indium-114m
solutions are available from laboratories recognised by the competent authority.
Radiochemical purity Examine by thin-layer chromatography (2.2.27) as described in the monograph on Radiopharmaceutical preparations (0125) using silica gel as the coating substance on a glassfibre sheet.
Apply to the plate 5 l of the solution to be examined. Develop immediately over a path of 15 cm
using a 9.0 g/l solution of sodium chloride R adjusted to pH 2.3 0.05 with dilute hydrochloric acid R.
Allow the plate to dry in a current of cold air. Determine the distribution of radioactivity using a
suitable detector. Indium-111 chloride migrates with an Rf value of 0.5 to 0.8. Not less than 95 per
cent of the total radioactivity of the chromatogram corresponds to indium-111 chloride.
Cadmium Not more than 0.40 g/ml, determined by electrothermal atomic absorption
spectrometry (Method I, 2.2.23).
Test solution. Dilute 0.05 ml of the solution to be examined to a suitable volume with a suitable
concentration of hydrochloric acid R.

70-36
Reference solutions. Prepare the reference solutions using cadmium standard solution (0.1 per cent Cd) R,
diluted as necessary with the same concentration of hydrochloric acid R as in the solution to be
examined.
Measure the absorbance at 228.8 nm using a cadmium hollow-cathode lamp as source of radiation.
Copper Not more than 0.15 g/ml, determined by electrothermal atomic absorption spectrometry
(Method I, 2.2.23).
Test solution. Dilute 0.1 ml the solution to be examined to a suitable volume with a suitable concentration of hydrochloric acid R.
Reference solutions. Prepare the reference solutions using copper standard solution (0.1 per cent) R
diluted as necessary with the same concentration of hydrochloric acid R as the solution to be examined.
Measure the absorbance at 324.8 nm using a copper hollow-cathode lamp as source of radiation.
Iron Not more than 0.60 g/ml, determined by electrothermal atomic absorption spectrometry
(Method I, 2.2.23).
Test solution. Dilute 0.1 ml of the solution to be examined to a suitable volume with a suitable
concentration of hydrochloric acid R.
Reference solutions. Prepare the reference solutions using iron standard solution (0.1 per cent Fe) R
diluted as necessary with the same concentration of hydrochloric acid R as the solution to be examined.
Measure the absorbance at 248.3 nm using an iron hollow-cathode lamp as source of radiation.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The solution may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised indium-111 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-37

Indium[111In] Oxine Solution


C27H18[111In]N3O3

547.2

Indium [111In] Oxine Solution complies with the requirements of the 3rd edition of the European
Pharmacopoeia [1109]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Indium (111In) oxine solution is a sterile solution of indium-111 in the form of a complex with 8hydroxyquinoline. It may contain suitable surface active agents and may be made isotonic by the
addition of sodium chloride and a suitable buffer. Indium-111 is a radioactive isotope of indium
and may be produced by the irradiation of cadmium with protons of suitable energy. The solution
contains not less than 90.0 per cent and not more than 110.0 per cent of the declared indium-111
radioactivity at the date and hour stated on the label. Not more than 0.25 per cent of the total
radioactivity is due to radionuclides other than indium-111. Not less than 90 per cent of the radioactivity corresponds to indium-111 complexed with oxine. The method of preparation is such that
no carrier is added and the specific radioactivity is not less than 1.85 GBq of indium-111 per
microgram of indium.
CHARACTERS
A clear, colourless solution.
Indium-111 has a half-life of 2.8 days and emits gamma radiation and X-rays.
IDENTIFICATION
A. Carry out the test after allowing sufficient time for short-lived impurities such as indium-110m to
decay. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised indium-111 solution apart from any differences due to the presence of
indium-114m, when measured either by direct comparison or by using an instrument calibrated
with the aid of such a solution. Standardised indium-111 and indium-114m solutions are available
from laboratories recognised by the competent authority. The most prominent gamma photons of
indium-111 have energies of 0.171 MeV and 0.245 MeV.
B. Place 5 mg to 10 mg of magnesium oxide R in a glass container of approximately 20 mm in internal
diameter. Add 20 l of the solution to be examined. Examine in ultraviolet light at 365 nm. Bright
yellow fluorescence is produced.
C. The distribution of radioactivity between the organic and aqueous phases in the test for radiochemical purity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 6.0 to 7.5.
Radionuclidic purity Record the gamma-ray and X-ray spectrum using a suitable instrument as
described in the monograph on Radiopharmaceutical preparations (0125). The spectrum does not
differ significantly from that of a standardised solution of indium-111, apart from any differences
due to the presence of indium-114m.
Indium-114m Carry out the test after allowing sufficient time for short-lived impurities such as indium-110m
to decay. Take a volume equivalent to 30 MBq and record the gamma-ray spectrum using a suitable
detector with a shield of lead, 6 mm thick, placed between the sample and the detector. The
response in the region corresponding to the 0.558 MeV photon and the 0.725 MeV photon of
indium-114m does not exceed that obtained using 75 kBq of a standardised solution of indium114m (0.25 per cent) measured under the same conditions, when all measurements are calculated
with reference to the date and hour of administration. (It should be noted that indium (111In) oxine
solution is a precursor used in the in vitro labelling of white blood cells or platelets prior to their reinjection into the patient. It is not intended for direct administration.) Standardised indium-111
and indium-114m solutions are available from laboratories recognised by the competent authority.
Radiochemical purity To a silanised separating funnel containing 3 ml of a 9 g/l solution of sodium
chloride R add 100 l of the solution to be examined and mix. Add 6 ml of octanol R and shake
vigorously. Allow the phases to separate and then run the lower layer into a suitable vial for
counting. Allow the upper layer to drain completely into a similar vial. Add 1 ml of octanol R to the
funnel, shake vigorously and drain into the vial containing the organic fraction. Add 5 ml of dilute
hydrochloric acid R to the funnel, shake vigorously and drain these rinsings into a third vial. Seal each
vial and, using a suitable instrument as described in the monograph on Radiopharmaceutical
preparations (0125), measure the radioactivity in each. Calculate the radiochemical purity by

70-38
expressing the radioactivity of the indium-111 oxine complex, found in the organic phase, as
a percentage of the radioactivity measured in the three solutions. Not less than 90 per cent of the
radioactivity corresponds to indium-111 complexed with oxine.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The solution may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised indium-111 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-39

Indium[111In] Pentetate Injection


Indium [111In] Pentetate Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0670]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Indium (111In) pentetate injection is a sterile and apyrogenic solution containing indium-111 in the
form of indium diethylenetriaminepenta-acetate. It may contain calcium and may be made isotonic
by the addition of sodium chloride and a suitable buffer. Indium-111 is a radioactive isotope of
indium which may be obtained by proton irradiation, of appropriate energy, of cadmium which
may be enriched with cadmium-111 or cadmium-112. The injection contains not less than 90 per
cent and not more than 110 per cent of the declared indium-111 radioactivity at the date and hour
stated on the label. The radioactivity due to indium-114m is not greater than 0.2 per cent of the
total radioactivity at the date and hour of administration. Not less than 95 per cent of the radioactivity corresponds to indium-111 complexed with pentetate.
CHARACTERS
A clear, colourless solution.
Indium-111 has a half-life of 2.8 days and emits gamma radiation and X-rays.
IDENTIFICATION
A. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised indium-111 solution apart from any differences due to the presence of
indium-114m, when measured either by direct comparison or by using an instrument calibrated
with the aid of such a solution. Standardised indium-111 and indium-114m solutions are available
from laboratories recognised by the competent authority. The most prominent gamma photons of
indium-111 have energies of 0.171 MeV and 0.245 MeV.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the injection is 7.0 to 8.0.
Radionuclidic purity Record the gamma-ray and X-ray spectrum using a suitable instrument as
described in the monograph on Radiopharmaceutical preparations (0125). The spectrum does not
differ significantly from that of a standardised solution of indium-111 apart from any differences
due to the presence of indium-114m.
Indium-114m Retain a sample of the injection to be examined for a sufficient time to allow the
indium-111 radioactivity to decay to a sufficiently low level to permit the detection of radionuclidic
impurities. Record the gamma-ray spectrum of the decayed material in a suitable instrument
calibrated with the aid of a standardised indium-114m solution. Indium-114m has a half-life of 49.5
days and its most prominent gamma photon has an energy of 0.190 MeV. The radioactivity due to
indium-114m is not greater than 0.2 per cent of the total radioactivity at the date and hour of
administration.
Radiochemical purity Examine by thin-layer chromatography (2.2.27) as described in the
monograph on Radiopharmaceutical preparations (0125), using silica gel as the coating substance on a
glass-fibre sheet. Heat the plate at 110C for 10 min. Use a plate such that during development the
mobile phase migrates over a distance of 10 cm to 15 cm in about 10 min.
Apply to the plate 5 l to 10 l of the injection to be examined and allow to dry. Develop over a
path of 10 cm to 15 cm using a 9 g/l solution of sodium chloride R. Allow the plate to dry in air.
Determine the distribution of radioactivity using a suitable detector. Indium pentetate complex
migrates near to the solvent front. The radioactivity of the spot corresponding to indium pentetate
complex represents not less than 95 per cent of the total radioactivity of the chromatogram.
Cadmium Not more than 5 g of Cd per millilitre, determined by atomic absorption spectrometry
(Method II, 2.2.23).
Test solution. Mix 0.1 ml of the injection to be examined with 0.9 ml of a mixture of 1 volume of
hydrochloric acid R and 99 volumes of water R.
Reference solutions. Prepare the reference solutions using cadmium standard solution (0.1 per cent Cd) R
and diluting with a mixture of 1 volume of hydrochloric acid R and 99 volumes of water R.
Measure the absorbance at 228.8 nm using a cadmium hollow-cathode lamp as source of radiation
and an air-acetylene flame.

70-40
Uncomplexed diethylenetriaminepenta-acetic acid In a micro test-tube, mix 100 l of the
injection to be examined with 100 l of a freshly prepared 1 g/l solution of hydroxynaphthol blue,
sodium salt R in 1M sodium hydroxide. Add 50 l of a 0.15 g/l solution of calcium chloride R. The
solution remains pinkish-violet or changes from blue to pinkish-violet (0.4 mg per millilitre).
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Bacterial endotoxins (2.6.14). Not more than 14/V I.U. of endotoxin per millilitre, V being the
maximum recommended dose in millilitres.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised indium-111 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-41

Iobenguane[123I] Injection
NH2
N
H

NH

[123I]
Iobenguane[123I] Injection complies with the requirements of the 3rd edition of the European Pharmacopoeia
[1113]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Iobenguane (123I) injection is a sterile, bacterial-endotoxin free solution of 1-(3-[123I]iodobenzyl)guanidine or its salts. It may contain a suitable buffer, a suitable labelling catalyst such as ionic
copper, a suitable labelling stabiliser such as ascorbic acid and antimicrobial preservatives. Iodine123 is a radioactive isotope of iodine and may be obtained by proton irradiation of xenon enriched
in xenon-124 (not less than 98 per cent) followed by the decay of caesium-123 formed via xenon123. The injection contains not less than 90.0 per cent and not more than 110.0 per cent of the
declared iodine-123 radioactivity at the date and hour stated on the label. Not less than 95 per cent
of the radioactivity corresponds to iodine-123 in the form of iobenguane. The specific radioactivity
is not less than 10 GBq of iodine-123 per gram of iobenguane base. Not more than 0.35 per cent
of the total radioactivity is due to radionuclides other than iodine-123.
CHARACTERS
A clear, colourless or slightly yellow solution.
Iodine-123 has a half-life of 13.2 h and emits gamma radiation and X-rays.
IDENTIFICATION
A. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised iodine-123 solution apart from any differences attributable to the
presence of iodine-125, tellurium-121 and other radionuclidic impurities. The most prominent
gamma photon of iodine-123 has an energy of 0.159 MeV. Iodine-125 has a half-life of 59.4 days
and emits an X-ray of 0.027 MeV and a photon of 0.035 MeV. Tellurium-121 has a half-life of
19.2 days and the most prominent photons have energies of 0.507 MeV and 0.573 MeV.
Standardised iodine-123, iodine-125 and tellurium-121 solutions are available from laboratories
recognised by the competent authority.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of the
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 3.5 to 8.0.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). Determine the relative amounts of
iodine-125, tellurium-121 and other radionuclidic impurities present. No radionuclides with longer
half-lives than iodine-125 are detected. For the determination of iodine-125, tellurium-121 and
other radionuclidic impurities, retain the solution to be examined for a sufficient time to allow the
radioactivity of iodine-123 to decrease to a level which permits the detection of radionuclidic
impurities. Record the gamma-ray spectrum and the X-ray spectrum of the decayed material using
a suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125). Not
more than 0.35 per cent of the total radioactivity is due to radionuclides other than iodine-123.
The injection may be released for use before completion of the test.
Radiochemical purity Examine by liquid chromatography (2.2.29).
Test solution. The injection to be examined.
Reference solution (a). Dissolve 0.100 g of sodium iodide R in the mobile phase and dilute to 100 ml
with the mobile phase.
Reference solution (b). Dissolve 20.0 mg of iobenguane sulphate CRS in 50 ml of the mobile phase and
dilute to 100.0 ml with the mobile phase.

70-42
The chromatographic procedure may be carried out using:
a stainless steel column 0.25 m long and 4.0 mm in internal diameter packed with silica gel for
chromatography R (5 m),
as mobile phase at a flow rate of 1.0 ml/min a mixture of 1 volume of an 80 g/l solution of
ammonium nitrate R, 2 volumes of dilute ammonia R2 and 27 volumes of methanol R,
a suitable radioactivity detector,
a spectrophotometer set at 254 nm and provided with a flow-cell,
a 10 l loop injector.
Inject the test solution and the reference solutions. Not less than 95 per cent of the radioactivity
of the chromatogram is found in the peak corresponding to iobenguane. Not more than 4 per cent
of the radioactivity is found in the peak corresponding to iodide and not more than 1 per cent of
the radioactivity is found in other peaks.
Specific radioactivity The specific radioactivity is calculated from the results obtained in the test
for radiochemical purity. Determine the content of iobenguane sulphate from the areas of the
peaks corresponding to iobenguane in the chromatograms obtained with the test solution and
reference solution (b). Calculate the concentration as iobenguane base by multiplying the result
obtained in the assay by 0.85.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Bacterial endotoxins (2.6.14). Not more than 175/V I.U. of endotoxin per millilitre, V being the
maximum recommended dose in millilitres.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125),
using a suitable counting apparatus by comparison with a standardised iodine-123 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
Store protected from light in the conditions prescribed in the monograph on Radiopharmaceutical
preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
The label states the specific radioactivity expressed in GBq of iodine-123 per gram of iobenguane
base.
__________________________________________________________________________________________________________ Ph Eur

70-43

Iobenguane[131I] Injection For Diagnostic Use


NH2
N
H

NH

[131I]
Iobenguane[131I] Injection For Diagnostic Use complies with the requirements of the 3rd edition of the
European Pharmacopoeia [1111]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Iobenguane (131I) injection for diagnostic use is a sterile, bacterial endotoxin-free solution of 1-(3[131I]iodobenzyl)guanidine or its salts. It may contain a suitable buffer. It may also contain a
suitable labelling catalyst such as ionic copper and a suitable labelling stabiliser such as ascorbic
acid. It may contain antimicrobial preservatives. Iodine-131 is a radioactive isotope of iodine and
may be obtained by neutron irradiation of tellurium or by extraction of uranium fission products.
The injection contains not less than 90.0 per cent and not more than 110.0 per cent of the
declared iodine-131 radioactivity at the date and hour stated on the label. Not less than 94 per cent
of the radioactivity corresponds to iodine-131 in the form of iobenguane. The specific radioactivity
is not less than 20 GBq of iodine-131 per gram of iobenguane base.
CHARACTERS
A clear, colourless or slightly yellow solution.
Iodine-131 has a half-life of 8.04 days and emits beta and gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised iodine-131 solution by direct comparison with such a solution. Standardised iodine131 solutions are available from laboratories recognised by the competent authority. The most
prominent gamma photon of iodine-131 has an energy of 0.365 MeV.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of the
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 3.5 to 8.0.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ
significantly from that of a standardised iodine-131 solution. Determine the relative amounts of
iodine-131, iodine-133, iodine-135 and other radionuclidic impurities present. Iodine-133 has a
half-life of 20.8 h and its most prominent gamma photons have energies of 0.530 MeV and 0.875
MeV. Iodine-135 has a half-life of 6.55 h and its most prominent gamma photons have energies of
0.527 MeV, 1.132 MeV and 1.260 MeV. Not less than 99.9 per cent of the total radioactivity is
due to iodine-131.
Radiochemical purity Examine by liquid chromatography (2.2.29).
Test solution. The injection to be examined.
Reference solution (a). Dissolve 0.100 g of sodium iodide R in the mobile phase and dilute to 100 ml
with the mobile phase.
Reference solution (b). Dissolve 20.0 mg of iobenguane sulphate CRS in 50 ml of the mobile phase and
dilute to 100.0 ml with the mobile phase.
The chromatographic procedure may be carried out using:
a stainless steel column 0.25 m long and 4.0 mm in internal diameter packed with silica gel for
chromatography R (5 m),
as mobile phase at a flow rate of 1.0 ml/min a mixture of 1 volume of an 80 g/l solution of
ammonium nitrate R, 2 volumes of dilute ammonia R2 and 27 volumes of methanol R,
a suitable radioactivity detector,
a spectrophotometer set at 254 nm and provided with a flow-cell,
a 10 l loop injector.

70-44
Inject the test solution and the reference solutions. Not less than 94 per cent of the radioactivity
of the chromatogram is found in the peak corresponding to iobenguane. Not more than 5 per cent
of the radioactivity is found in the peak corresponding to iodide and not more than 1 per cent of
the radioactivity is found in other peaks.
Specific radioactivity The specific radioactivity is calculated from the results obtained in the test
for radiochemical purity. Determine the content of iobenguane sulphate from the areas of the
peaks corresponding to iobenguane in the chromatograms obtained with the test solution and
reference solution (b). Calculate the concentration as iobenguane base by multiplying the result
obtained in the assay by 0.85.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Bacterial endotoxins (2.6.14). Not more than 175/V I.U. of endotoxin per millilitre, V being the
maximum recommended dose in millilitres.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125),
using a suitable counting apparatus by comparison with a standardised iodine-131 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
Store protected from light in the conditions prescribed in the monograph on Radiopharmaceutical
preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
The label states the specific radioactivity expressed in giga-becquerels of iodine-131 per gram of
iobenguane base.
__________________________________________________________________________________________________________ Ph Eur

70-45

Iobenguane[131I] Injection for Therapeutic Use


NH2
N
H

NH

[131I]
Iobenguane[131I] Injection for Therapeutic Use complies with the requirements of the 3rd edition of the
European Pharmacopoeia [1112]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Iobenguane (131I) injection for therapeutic use is a sterile, bacterial endotoxin-free solution of 1-(3[131I]iodobenzyl)guanidine or its salts. It may contain a suitable buffer, a suitable labelling catalyst
such as ionic copper, a suitable labelling stabiliser such as ascorbic acid and antimicrobial
preservatives. Iodine-131 is a radioactive isotope of iodine and may be obtained by neutron
irradiation of tellurium or by extraction of uranium fission products. The injection contains not less
than 90.0 per cent and not more than 110.0 per cent of the declared iodine-131 radioactivity at the
date and hour stated on the label. Not less than 92 per cent of the radioactivity corresponds to
iodine-131 in the form of iobenguane. The specific radioactivity is not less than 400 GBq of iodine131 per gram of iobenguane base.
CHARACTERS
A clear, colourless or slightly yellow solution.
Iodine-131 has a half-life of 8.04 days and emits beta and gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised iodine-131 solution by direct comparison with such a solution. Standardised iodine131 solutions are available from laboratories recognised by the competent authority. The most
prominent gamma photon of iodine-131 has an energy of 0.365 MeV.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of the
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 3.5 to 8.0.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ
significantly from that of a standardised iodine-131 solution. Determine the relative amounts of
iodine-131, iodine-133, iodine-135 and other radionuclidic impurities present. Iodine-133 has a
half-life of 20.8 h and its most prominent gamma photons have energies of 0.530 MeV and 0.875
MeV. Iodine-135 has a half-life of 6.55 h and its most prominent gamma photons have energies of
0.527 MeV, 1.132 MeV and 1.260 MeV. Not less than 99.9 per cent of the total radioactivity is
due to iodine-131.
Radiochemical purity Examine by liquid chromatography (2.2.29).
Test solution. The injection to be examined.
Reference solution (a). Dissolve 0.100 g of sodium iodide R in the mobile phase and dilute to 100 ml
with the mobile phase.
Reference solution (b). Dissolve 20.0 mg of iobenguane sulphate CRS in 50 ml of the mobile phase and
dilute to 100.0 ml with the mobile phase.
The chromatographic procedure may be carried out using:
a stainless steel column 0.25 m long and 4.0 mm in internal diameter packed with silica gel for
chromatography R (5 m),
as mobile phase at a flow rate of 1.0 ml/min a mixture of 1 volume of an 80 g/l solution of
ammonium nitrate R, 2 volumes of dilute ammonia R2 and 27 volumes of methanol R,
a suitable radioactivity detector,
a spectrophotometer set at 254 nm and provided with a flow-cell,
a 10 l loop injector.

70-46
Inject the test solution and the reference solutions. Not less than 92 per cent of the radioactivity
of the chromatogram is found in the peak corresponding to iobenguane. Not more than 7 per cent
of the radioactivity is found in the peak corresponding to iodide and not more than 1 per cent of
the radioactivity is found in other peaks.
Specific radioactivity The specific radioactivity is calculated from the results obtained in the test
for radiochemical purity. Determine the content of iobenguane sulphate from the areas of the
peaks corresponding to iobenguane in the chromatograms obtained with the test solution and
reference solution (b). Calculate the concentration as iobenguane base by multiplying the result
obtained in the assay by 0.85.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Bacterial endotoxins (2.6.14). Not more than 175/V I.U. of endotoxin per millilitre, V being the
maximum recommended dose in millilitres.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125),
using a suitable counting apparatus by comparison with a standardised iodine-131 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
Store protected from light in the conditions prescribed in the monograph on Radiopharmaceutical
preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
The label states the specific radioactivity expressed in gigabecquerels of iodine-131 per gram of
iobenguane base.
__________________________________________________________________________________________________________ Ph Eur

70-47

Dried Iodinated [125I] Fibrinogen


Dried Iodinated [125I] Fibrinogen complies with the requirements of the 3rd edition of the European
Pharmacopoeia for Dried Human Iodinated[125I] Fibrinogen [0604]. These requirements are reproduced after
the heading 'Definition' below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Dried iodinated (125I) human fibrinogen is a sterile, apyrogenic preparation of human fibrinogen
which has been labelled with iodine-125. The human fibrinogen is prepared from plasma that
complies with the monograph on Human plasma for fractionation (0853).
The method of preparation is designed to avoid the transmission of or to inactivate known agents
of infection and to give a final product with a fibrinogen content not less than 80 per cent of the
total protein content. The preparation may contain additives such as sodium citrate and human
albumin.
The reconstituted preparation contains not less than 85.0 per cent and not more than 115.0 per
cent of the declared iodine-125 radioactivity at the date stated on the label. Not less than 95 per
cent of the radioactivity is due to iodine-125 bound to protein and not less than 80 per cent of the
total radioactivity is due to substances bound to clottable protein. Not more than 1.0 per cent of
the total radioactivity is due to iodine-126.
CHARACTERS
A white or pale yellow powder or friable solid.
Iodine-125 has a half-life of 60.1 days and emits gamma radiation and X-rays.
IDENTIFICATION
A. Record the gamma-ray and X-ray spectrum of the reconstituted preparation using a suitable
instrument as described in the monograph on Radiopharmaceutical preparations (0125). The spectrum
does not differ significantly from that of a standardised iodine-125 solution, apart from any
differences attributable to the presence of iodine-126. Standardised iodine-125 and caesium-137
solutions are available from laboratories recognised by the competent authority. The most
prominent photon of the preparation has an energy of 0.027 MeV, corresponding to the X-ray of
tellurium. Iodine-126 has a half-life of 13.0 days and its most prominent gamma photons have
energies of 0.388 MeV and 0.666 MeV.
B. Using a suitable range of species-specific antisera, carry out precipitation tests on the
reconstituted preparation. The test is to be carried out using antisera specific for the plasma
proteins of each species of domestic animal currently in use for the preparation of materials of
biological origin in the country concerned. The preparation is shown to contain proteins of human
origin and gives negative results with antisera specific to plasma proteins of other species.
C. The test for clottability also contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the reconstituted preparation is 6.0 to 8.5.
Iodine-126 Record the gamma-ray and X-ray spectrum of the reconstituted preparation using a
suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125) in
comparison with standardised solutions of iodine-125 and caesium-137. Determine the relative
amounts of iodine-125 and iodine-126 present on the assumption that the 0.666 MeV gamma
photon of iodine-126 is emitted in 33 per cent of disintegrations and that the 0.661 MeV gamma
photon of caesium-137 is emitted in 85.4 per cent of disintegrations.
Radiochemical purity Examine the reconstituted preparation by zone electrophoresis (2.2.31),
using a paper strip 200 mm long as the support and phosphate buffer pH 6.4 R as the electrolyte
solution. Apply to the paper 10 l of the reconstituted preparation as a band 3 mm wide at a
position 100 mm from the anode. Apply an electric potential of about 200 V for 60 min using a
stabilised current. Allow the strip to dry. Determine the distribution of radioactivity using a suitable
detector. Iodide ion moves about 7 cm towards the anode and iodinated fibrinogen remains almost
at the starting point. The radioactivity due to iodine-125 bound to protein represents not less than
95 per cent of the total radioactivity of the electrophoretogram.
Clottability To 0.2 ml of the reconstituted preparation add 5 ml of human plasma, mix and after
mixing transfer 1 ml of the mixture to each of two vials each containing 2 ml of phosphate buffer pH
6.4 R. Add to one of the vials 0.1 ml of a solution containing 10 units of bovine thrombin R. (One unit
of thrombin will clot a 2.5 g/l of fibrinogen (>90 per cent clottable) in 15 s at 37C.) Mix the
contents of this vial thoroughly with a glass defibrinating rod and allow to stand for not less than

70-48
1 h without removing the rod. Remove the clot from the vial using the glass rod and discard both.
Take 1 ml of the remaining solution and 1 ml of the control solution to which no bovine thrombin
has been added. Measure the radioactivity of each and determine the percentage of radioactivity
removed in the clot.
Not less than 80 per cent of the total radioactivity is present in the clot.
Sterility The reconstituted preparation complies with the test for sterility prescribed in the
monograph on Radiopharmaceutical preparations (0125). The preparation may be released for use
before completion of the test.
Bacterial endotoxins Dissolve the content of one vial in a suitable volume (V ml) of the
prescribed solvent. The maximum allowable endotoxin concentration is 175/V I.U. of
endotoxin per millilitre.
RADIOACTIVITY
Measure the radioactivity of the reconstituted preparation as described in the monograph on
Radiopharmaceutical preparations (0125), using suitable counting equipment by comparison with a
standardised iodine-125 solution or by measurement in an instrument calibrated with the aid of
such a solution. Use an instrument incorporating a scintillation detector such as a thin sodium
iodide crystal and set the instrument so that the contribution from the radioactivity of iodine-126 is
minimised.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
The label states:
the method of reconstitution,
that the preparation should be used immediately after reconstitution.
__________________________________________________________________________________________________________ Ph Eur

70-49

Iodinated[131I] Norcholesterol Injection


Iodinated[131I] Norcholesterol Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0939]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Iodinated (131I) norcholesterol injection is a sterile, bacterial endotoxin-free solution of
6b-[131I]iodomethyl-19-norcholest-5(10)-en-3b-ol. It may contain a suitable emulsifier such as
polysorbate 80 and a suitable antimicrobial preservative such as benzyl alcohol. Iodine-131 is a
radioactive isotope of iodine and may be obtained by neutron irradiation of tellurium or by
extraction from uranium fission products. The injection contains not less than 90.0 per cent and
not more than 110.0 per cent of the declared iodine-131 radioactivity at the date and hour stated
on the label. Not less than 85 per cent of the radioactivity corresponds to iodine-131 in the form of
6b-[131I]iodomethyl-19-norcholest-5(10)-en-3b-ol. Not more than 5 per cent of the radioactivity
corresponds to iodine-131 in the form of iodide. The specific radioactivity is 3.7 GBq to 37
GBq per gram of 6b-iodomethylnorcholesterol.
CHARACTERS
A clear or slightly turbid, colourless or pale yellow solution.
Iodine-131 has a half-life of 8.04 days and emits beta and gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised iodine-131 solution by direct comparison with such a solution. The most prominent
photon of iodine-131 has an energy of 0.365 MeV. Standardised iodine-131 solutions are available
from laboratories recognised by the competent authority.
B. Examine the chromatogram obtained in test (a) for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is between 3.5 and 8.5.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ
significantly from that of a standardised iodine-131 solution. Determine the relative amounts of
iodine-131, iodine-133, iodine-135 and other radionuclidic impurities present. Iodine-133 has a
half-life of 20.8 h and its most prominent gamma photons have energies of 0.530 MeV and
0.875 MeV. Iodine-135 has a half-life of 6.55 h and its most prominent gamma photons have
energies of 0.527 MeV, 1.132 MeV and 1.260 MeV. Not less than 99.9 per cent of the total radioactivity is due to iodine-131.
Radiochemical purity
(a) Examine by thin-layer chromatography (2.2.27) as described in the monograph on Radiopharmaceutical preparations (0125) using silica gel GF254 R as the coating substance.
Test solution. The injection to be examined.
Carrier solution. Dissolve 10 mg of potassium iodide R, 20 mg of potassium iodate R and 0.1 g of sodium
hydrogen carbonate R in distilled water R and dilute to 10 ml with the same solvent.
Apply to the plate up to 5 l of the test solution and 10 l of the carrier solution on the same spot.
Develop over a path of 15 cm (about 60 min) using chloroform R. Allow the plate to dry in air and
examine in ultraviolet light at 254 nm. Determine the distribution of radioactivity using a suitable
detector. In the chromatogram obtained, not less than 85 per cent of the total radioactivity is
found in the spot corresponding to 6b-iodomethyl-19-norcholest-5(10)-en-3b-ol at an Rf value of
about 0.5. Iodide ion remains near the starting-line.
(b) Examine by thin-layer chromatography (2.2.27) as described in the monograph on Radiopharmaceutical preparations (0125) using silica gel GF254 R as the coating substance.
Test solution. The injection to be examined.
Carrier solution. Dissolve 10 mg potassium iodide R, 20 mg of potassium iodate R and 0.1 g of sodium
hydrogen carbonate R in distilled water R and dilute to 10 ml with the same solvent.
Apply to the plate 10 l of the carrier solution and then up to 5 l of the test solution on the same
spot. Develop over a path of 15 cm (about 90 min) using a mixture of equal volumes of chloroform R
and ethanol R. Allow the plate to dry in air. Expose the plate to ultraviolet light at 254 nm for 5 min.

70-50
A yellow spot corresponding to iodide develops at an Rf value of about 0.5. Determine the
distribution of radioactivity using a suitable detector. The main peak of radioactivity is near to the
solvent front. Other iodocholesterols migrate near the solvent front. In the chromatogram
obtained, not more than 5 per cent of the total radioactivity is found in the spot corresponding to
iodide.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Bacterial endotoxins (2.6.14). Not more than 175/V I.U. of endotoxin per millilitre, V being the
maximum recommended dose in millilitres.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised iodine-131 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
Store protected from light at a temperature not exceeding 18C in the conditions prescribed in the
monograph on Radiopharmaceutical preparations (0125).
LABELLING
See the Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-51

Krypton[81mKr] Inhalation Gas


1/01
Krypton[81mKr] Inhalation Gas complies with the requirements of the 3rd edition of the European
Pharmacopoeia [1533]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Krypton (81mKr) inhalation gas is a mixture of krypton-81m and a suitable vehicle such as air.
Krypton-81m is formed by decay of its parent radionuclide rubidium-81. Rubidium-81 has a
half-life of 4.58 h.
The krypton-81m formed is separated from the rubidium-81 with a flow of a suitable gas in a
rubidium/krypton generator. Rubidium-81 is produced by proton irradiation of krypton isotopes or
by helium-3 or helium-4 irradiation of bromine. After separation of rubidium-81 from the target, it
is retained by a suitable support.
Krypton-81m is eluted at a suitable flow rate with a vehicle such as air. The level of moisture
required in the eluent depends on the type of generator used. The transport tube for
administration has a defined length and inner diameter. The radioactivity concentration is determined before administration.
The radioactivity due to radionuclides other than krypton-81m is not greater than 0.1 per cent,
expressed as a percentage of the total radioactivity in the preparation and calculated with reference
to the date and time of administration.
CHARACTERS
A clear, colourless gas.
Krypton-81m has a half-life of 13.1 s and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The gamma photon of krypton-81m has an
energy of 0.190 MeV.
B. The half-life determined as described in the monograph on Radiopharmaceutical preparations
(0125) is 11.8 s to 14.4 s.
TESTS
Radionuclidic purity
Elute the generator as prescribed. Pass a sufficient amount (2 litres to 10 litres) of eluate at a
suitable flow rate through a suitable absorber such as water. Determine the amount of radioactivity
eluted. Allow the krypton-81m to decay for 5 min and record the gamma and X-ray spectrum of
the residual radioactivity on the absorber using a suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125). Examine the gamma-ray and X-ray spectrum of
the absorber for the presence of radioactive impurities, which must be identified and quantified.
The absorbed radioactivity is not more than 0.1 per cent of the radioactivity passed through the
absorber, calculated with reference to the date and time of administration.
RADIOACTIVITY
Determine the radioactive concentration of the preparation as described in the monograph
on Radiopharmaceutical preparations (0125) using suitable equipment such as an ionisation chamber
or a gamma ray spectrometer. The measurement equipment may be calibrated by reference to a
primary calibrated instrument at a laboratory recognised by the competent authority. The radioactivity is measured under defined operating conditions, such as gas flow rate and measurement
geometry, that are identical to those used for the calibration of the instrument.
STORAGE
The storage conditions apply to the generator and are described in the monograph on Radiopharmaceutical preparations (0125).
LABELLING
The labelling conditions apply to the generator and are described in the monograph on Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

70-52

Sodium Chromate[51Cr] Sterile Solution


Sodium Chromate[51Cr] Sterile Solution complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0279]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Sodium chromate (51Cr) sterile solution is a sterile solution of sodium (51Cr) chromate made
isotonic by the addition of sodium chloride. Chromium-51 is a radioactive isotope of chromium
and may be prepared by neutron irradiation of chromium, either of natural isotopic composition or
enriched in chromium-50. The solution contains not less than 90.0 per cent and not more than
110.0 per cent of the declared chromium-51 radioactivity at the date and hour stated on the label.
Not less than 90 per cent of the radioactivity corresponds to chromium-51 in the form of
chromate. The specific radioactivity is not less than 370 MBq of chromium-51 per milligram of
chromate ion.
CHARACTERS
A clear, colourless or slightly yellow solution.
Chromium-51 has a half-life of 27.7 days and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised chromium-51 solution. Standardised chromium-51 solution are available from
laboratories recognised by the competent authority. The gamma photon has an energy of
0.320 MeV.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 6.0 to 8.5.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ
significantly from that of a standardised chromium-51 solution.
Radiochemical purity Examine by ascending paper chromatography (2.2.26), as described in the
monograph on Radiopharmaceutical preparations (0125).
Apply to the paper a quantity of the solution sufficient for the detection method. Begin the
development immediately and develop for 2.5 h using a mixture of 25 volumes of ammonia R, 50
volumes of alcohol R and 125 volumes of water R. Chromic ions remain on the starting line. Determine the distribution of the radioactivity using a suitable detector. Not less than 90 per cent of the
total radioactivity of the chromatogram is found in the spot with an Rf value of about 0.9, corresponding to sodium chromate.
Total chromate Not more than 2.7 g of chromate ion (CrO42) per megabecquerel. Measure the
absorbance of the solution (2.2.25) at the absorption maximum at 370 nm. Calculate the content of
chromate using the absorbance of a standard consisting of a 1.7 mg/l solution of potassium
chromate R. If necessary, adjust the solution to be examined and the standard to pH 8.0 by adding
sodium hydrogen carbonate solution R.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The solution may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised chromium-51 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
_______________________________________________________________________________________________________________________ Ph Eur

70-53

Sodium Iodide[131I] Capsules for Diagnostic Use


Sodium Iodide[131I] Capsules for Diagnostic Use comply with the requirements of the 3rd edition of the
European Pharmacopoeia [0938]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Sodium iodide (131I) capsules for diagnostic use contain iodine-131 in the form of sodium iodide on
a suitable solid support. The capsules also contain sodium thiosulphate or other reducing agents
and may contain a suitable buffer. Iodine-131 is a radioactive isotope of iodine obtained by
neutron irradiation of tellurium or by extraction from uranium fission products. Each capsule
contains not less than 90.0 per cent and not more than 110.0 per cent of the declared iodine-131
radioactivity at the date and hour stated on the label. Not more than 0.1 per cent of the total
radioactivity is due to radionuclides other than iodine-131. Not less than 95 per cent of the radioactivity corresponds to iodine-131 in the form of iodide. The method of preparation is such that
the specific radioactivity is not less than 185 GBq of iodine-131 per milligram of iodine. The
capsules comply with the requirements for hard capsules in the monograph on Capsules (0016),
unless otherwise justified and authorised.
CHARACTERS
Iodine-131 has a half-life of 8.04 days and emits beta and gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised iodine-131 solution. Standardised iodine-131 solutions are available from laboratories
recognised by the competent authority. The most prominent gamma photon of iodine-131 has an
energy of 0.365 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
TESTS
Radionuclidic purity Use a suitable volume of the solution obtained in the test for
disintegration. Record the gamma-ray spectrum using a suitable instrument as described in the
monograph Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from
that of a standardised iodine-131 solution.
Determine the relative amounts of iodine-131, iodine-133, iodine-135 and other radionuclidic
impurities present. Iodine-133 has a half-life of 20.8 h and its most prominent gamma photons
have energies of 0.530 MeV and 0.875 MeV. Iodine-135 has a half-life of 6.55 h and its most
prominent gamma photons have energies of 0.527 MeV, 1.132 MeV and 1.260 MeV. Not less than
99.9 per cent of the total radioactivity is due to iodine-131.
Radiochemical purity Examine by ascending paper chromatography (2.2.26), as described in the
monograph on Radiopharmaceutical preparations (0125).
Test solution. Dissolve the contents of one capsule to be examined in 5 ml of water R.
On a strip of suitable paper apply 10 l of the test solution. Add on the same spot, without
previously drying, 10 l of a solution containing 1 g/l of potassium iodide R, 2 g/l of potassium iodate R
and 10 g/l of sodium hydrogen carbonate R. Develop without previously drying over a path of 10 cm
using a mixture of 30 volumes of water R and 70 volumes of methanol R. Allow to dry and determine
the radioactivity using a suitable detector. In the chromatogram obtained, not less than 95 per cent
of the total radioactivity is found in the spot corresponding to iodide. Spray the paper with
palladium chloride solution R and heat the paper in a current of hot air. Iodide forms a brown spot;
iodate forms a yellow spot after heating.
Disintegration In a water-bath at 37C, warm in a small beaker 10 ml of a 2.0 g/l solution of
potassium iodide R. Add one of the capsules to be examined. Stir magnetically at a rotation rate of 20
revolutions per minute. The shell and its contents dissolve completely within 15 min.
Uniformity of content Determine by measuring in a suitable counting assembly and under
identical geometrical conditions, the radioactivity of each of not less than ten capsules. Calculate
the average radioactivity per capsule. The radioactivity of no capsule differs by more than 10 per
cent from the average. The relative standard deviation is not greater than 3.5 per cent.
RADIOACTIVITY
The average radioactivity determined in the test for uniformity of content is not less than 90.0 per
cent and not more than 110.0 per cent of the declared iodine-131 radioactivity at the date and

70-54
hour stated on the label.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
_______________________________________________________________________________________________________________________ Ph Eur

70-55

Sodium Iodide[123I] Solution


Sodium Iodide[123I] Solution complies with the requirements of the 3rd edition of the European Pharmacopoeia
[0563]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Sodium iodide (123I) solution is a solution for oral administration containing iodine-123 in the form
of sodium iodide; it also contains sodium thiosulphate or some other suitable reducing agent and
may contain a suitable buffer. Iodine-123 is a radioactive isotope of iodine and may be obtained by
proton irradiation of xenon enriched in xenon-124 (not less than 98 per cent) followed by the
decay of caesium-123 formed via xenon-123. The solution contains not less than 90.0 per cent and
not more than 110.0 per cent of the declared iodine-123 radioactivity at the date and hour stated
on the label. Not less than 95 per cent of the radioactivity corresponds to iodine-123 in the form of
iodide. The specific radioactivity is not less than 185 GBq of iodine-123 per milligram of iodine.
Not more than 0.35 per cent of the total radioactivity is due to radionuclides other than iodine123.
CHARACTERS
A clear, colourless solution.
Iodine-123 has a half-life of 13.2 h and emits gamma radiation and X-rays.
IDENTIFICATION
A. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised iodine-123 solution apart from any differences attributable to the
presence of iodine-125, tellurium-121 and other radionuclidic impurities. Standardised iodine-123,
iodine-125 and tellurium-121 solutions are available from laboratories recognised by the
competent authority. The most prominent gamma photon of iodine-123 has an energy of
0.159 MeV and is accompanied by an X-ray of 0.027 MeV. Iodine-125 has a half-life of 59.4 days
and emits an X-ray of 0.027 MeV and a photon of 0.035 MeV. Tellurium-121 has a half-life of
19.2 days and the most prominent photons have energies of 0.507 MeV and 0.573 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 7.0 to 10.0.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). Determine the relative amounts of
iodine-125, tellurium-121 and other radionuclidic impurities present. No radionuclides with longer
half lives than iodine-125 are detected. For the determination of iodine-125, tellurium-121 and
other radionuclidic impurities, retain the solution to be examined for a sufficient time to allow the
radioactivity of iodine-123 to decrease to a level which permits the detection of radionuclidic
impurities. Record the gamma-ray spectrum and X-ray spectrum of the decayed material using a
suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125). Not
more than 0.35 per cent of the total radioactivity is due to radionuclides other than iodine-123.
The solution may be released for use before completion of the test.
Radiochemical purity Examine by ascending paper chromatography (2.2.26), as described in the
monograph on Radiopharmaceutical preparations (0125).
Test solution. Dilute the preparation to be examined with water R until the radioactivity is equivalent
to about 20,000 counts per minute per 10 l. Add an equal volume of a solution containing 1 g/l of
potassium iodide R, 2 g/l of potassium iodate R and 10 g/l of sodium hydrogen carbonate R and mix.
Reference solution (a). Dissolve 0.1 g of potassium iodide R in water R and dilute to 10 ml with the same
solvent.
Reference solution (b). Dissolve 0.2 g of potassium iodate R in water R and dilute to 10 ml with the same
solvent.
On a strip of suitable paper 250 mm long apply separately 20 l of the test solution, 10 l of
reference solution (a) and 10 l of reference solution (b). Develop over a path of 20 cm (about
2 h) using a mixture of 10 volumes of water R and 30 volumes of methanol R. Allow the paper to dry
in air and determine the positions of the inactive potassium iodide and potassium iodate by the
application of filter papers impregnated respectively with acetic acid R and potassium iodate R and
acetic acid R and potassium iodide R. Determine the distribution of radioactivity using a suitable
detector. In the chromatogram obtained with the test solution, not less than 95 per cent of the total

70-56
radioactivity is found in the spot corresponding to iodide and the R value of the spot does not
differ by more than 5 per cent from the R value of the spot corresponding to inactive iodide in the
chromatogram obtained with reference solution (a).
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised iodine-123 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
_______________________________________________________________________________________________________________________ Ph Eur

70-57

Sodium Iodide[125I] Solution


Sodium Iodide[125I] Solution complies with the requirements of the 3rd edition of the European Pharmacopoeia
[0280]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Sodium iodide (125I) solution is a solution for oral administration containing iodine-125 in the form
of sodium iodide; it also contains sodium thiosulphate or some other suitable reducing agent and
may contain a suitable buffer. Iodine-125 is a radioactive isotope of iodine and may be prepared by
neutron irradiation of xenon. The solution contains not less than 85.0 per cent and not more than
115.0 per cent of the declared iodine-125 radioactivity at the date stated on the label. Not less than
95 per cent of the radioactivity corresponds to iodine-125 in the form of iodide. The method of
preparation is such that the specific radioactivity is not less than 74 GBq of iodine-125 per
milligram of iodine at the date stated on the label. Not more than 1.0 per cent of the total radioactivity is due to iodine-126.
CHARACTERS
A clear, colourless solution.
Iodine-125 has a half-life of 60.1 days and emits gamma radiation and X-rays.
IDENTIFICATION
A. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised iodine-125 solution, apart from any differences attributable to the
presence of iodine-126. Standardised iodine-125 and caesium-137 solutions are available from
laboratories recognised by the competent authority. The most prominent photon of the
preparation has an energy of 0.027 MeV, corresponding to the X-ray of tellurium. Iodine-126 has
a half-life of 13.0 days and its presence is shown by its most prominent gamma photons with
energies of 0.388 MeV and 0.666 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 7.0 to 10.0.
Iodine-126 Record the gamma-ray and X-ray spectrum as described in the monograph on Radiopharmaceutical preparations (0125) using a suitable instrument in comparison with standardised
solutions of iodine-125 and caesium-137. Determine the relative amounts of iodine-125 and
iodine-126 present on the assumption that the 0.666 MeV gamma photon of iodine-126 is emitted
in 33 per cent of disintegrations, and that the 0.661 MeV gamma photon of caesium-137 is emitted
in 85.4 per cent of disintegrations.
Radiochemical purity Examine by ascending paper chromatography (2.2.26), as described in the
monograph on Radiopharmaceutical preparations (0125).
Test solution. Dilute the preparation to be examined with water R until the radioactivity is equivalent
to about 20,000 counts per minute per 10 l. Add an equal volume of a solution containing 1 g/l of
potassium iodide R, 2 g/l of potassium iodate R and 10 g/l of sodium hydrogen carbonate R and mix.
Reference solution (a). Dissolve 0.1 g of potassium iodide R in water R and dilute to 10 ml with the same
solvent.
Reference solution (b). Dissolve 0.2 g of potassium iodate R in water R and dilute to 10 ml with the same
solvent.
Apply separately to a strip of paper 250 mm long 20 l of the test solution, 10 l of reference
solution (a) and 10 l of reference solution (b). Develop over a path of 20 cm using a mixture of 10
volumes of water R and 30 volumes of methanol R (the development time is about 2 h). Allow the
paper to dry in air and determine the positions of the inactive potassium iodide and potassium
iodate by the application of filter papers impregnated respectively with acetic acid R and potassium
iodate R and acetic acid R and potassium iodide R. Determine the distribution of radioactivity using a
suitable detector. In the chromatogram obtained with the test solution, not less than 95 per cent of
the total radioactivity is found in the spot corresponding to iodide and the Rf value of the spot does
not differ by more than 5 per cent from the Rf value of the spot corresponding to inactive
potassium iodide in the chromatogram obtained with reference solution (a).
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)

70-58
using suitable counting equipment by comparison with a standardised iodine-125 solution or by
measurement in an instrument calibrated with the aid of such a solution. Use an instrument
incorporating a scintillation detector such as a thin sodium iodide crystal and set the instrument so
that the contribution from the radioactivity of iodine-126 is minimised.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
_______________________________________________________________________________________________________________________ Ph Eur

70-59

Sodium Iodide[131I] Solution


Sodium Iodide[131I] Solution complies with the requirements of the 3rd edition of the European Pharmacopoeia
[0281]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Sodium iodide (131I) solution is a solution for oral administration containing iodine-131 in the form
of sodium iodide; it also contains sodium thiosulphate or some other suitable reducing agent and
may contain a suitable buffer. Iodine-131 is a radioactive isotope of iodine and may be obtained by
neutron irradiation of tellurium or by extraction from uranium fission products. The solution
contains not less than 90.0 per cent and not more than 110.0 per cent of the declared iodine-131
radioactivity at the date and hour stated on the label. Not more than 0.1 per cent of the total
radioactivity is due to radionuclides other than iodine-131. Not less than 95 per cent of the radioactivity corresponds to iodine-131 in the form of iodide. The method of preparation is such that
the specific radioactivity is not less than 185 GBq of iodine-131 per milligram of iodine at the date
and hour stated on the label.
CHARACTERS
A clear, colourless solution.
Iodine-131 has a half-life of 8.04 days and emits beta and gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised iodine-131 solution. Standardised iodine-131 solutions are available from laboratories
recognised by the competent authority. The most prominent gamma photon of iodine-131 has an
energy of 0.365 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 7.0 to 10.0.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ
significantly from that of a standardised iodine-131 solution. Determine the relative amounts of
iodine-131, iodine-133, iodine-135 and other radionuclidic impurities present. Iodine-133 has a
half-life of 20.8 h and its most prominent gamma photons have energies of 0.53 MeV and
0.875 MeV. Iodine-135 has a half-life of 6.55 h and its most prominent gamma photons have
energies of 0.527 MeV and 1.260 MeV. Not less than 99.9 per cent of the total radioactivity is due
to iodine-131 and not more than 0.1 per cent of the total radioactivity is due to iodine-133, iodine135 and other radionuclidic impurities.
Radiochemical purity Examine by ascending paper chromatography (2.2.26), as described in the
monograph on Radiopharmaceutical preparations (0125).
Test solution. Dilute the preparation to be examined with water R until the radioactivity is equivalent
to about 20,000 counts per minute per 10 l. Add an equal volume of a solution containing 1 g/l of
potassium iodide R, 2 g/l of potassium iodate R and 10 g/l of sodium hydrogen carbonate R and mix.
Reference solution (a). Dissolve 0.1 g of potassium iodide R in water R and dilute to 10 ml with the same
solvent.
Reference solution (b). Dissolve 0.2 g of potassium iodate R in water R and dilute to 10 ml with the same
solvent.
Apply separately to a strip of paper 250 mm long 20 l of the test solution, 10 l of reference
solution (a) and 10 l of reference solution (b). Develop over a path of 20 cm using a mixture of 10
volumes of water R and 30 volumes of methanol R (the development time is about 2 h). Allow the
paper to dry in air and determine the positions of the inactive potassium iodide and potassium
iodate by the application of filter papers impregnated respectively with acetic acid R and potassium
iodate R and acetic acid R and potassium iodide R. Determine the distribution of radioactivity using a
suitable detector. In the chromatogram obtained with the test solution, not less than 95 per cent of
the total radioactivity is found in the spot corresponding to iodide and the Rf value of the spot does
not differ by more than 5 per cent from that of the spot corresponding to inactive potassium iodide
in the chromatogram obtained with reference solution (a).

70-60
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised iodine-131 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
_______________________________________________________________________________________________________________________ Ph Eur

70-61

Sodium Iodohippurate[123I] Injection


Sodium Iodohippurate[123I] Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0564]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Sodium iodohippurate (123I) injection is a sterile solution of sodium (2-[123I]iodobenzamido)acetate. It may contain a suitable buffer and a suitable antimicrobial preservative such as benzyl
alcohol. Iodine-123 is a radioactive isotope of iodine and may be obtained by proton irradiation of
xenon enriched in xenon-124 (not less than 98 per cent) followed by the decay of caesium-123
formed via xenon-123. The injection contains not less than 90.0 per cent and not more than
110.0 per cent of the declared iodine-123 radioactivity at the date and hour stated on the label.
Not less than 96 per cent of the radioactivity corresponds to iodine-123 in the form of sodium 2iodohippurate. The specific radioactivity is 0.74 GBq to 10.0 GBq of iodine-123 per gram of
sodium 2-iodohippurate. Not more than 0.35 per cent of the total radioactivity is due to radionuclides other than iodine-123.
CHARACTERS
A clear, colourless liquid.
Iodine-123 has a half-life of 13.2 h and emits gamma radiation and X-rays.
IDENTIFICATION
A. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised iodine-123 solution apart from any differences attributable to the
presence of iodine-125, tellurium-121 and other radionuclidic impurities. Standardised iodine-123,
iodine-125 and tellurium-121 solutions are available from laboratories recognised by the national
authorities. The most prominent gamma photon of iodine-123 has an energy of 0.159 MeV and is
accompanied by an X-ray of 0.027 MeV. Iodine-125 has a half-life of 59.4 days and emits an X-ray
of 0.027 MeV and a photon of 0.035 MeV. Tellurium-121 has a half-life of 19.2 days and the most
prominent photons have energies of 0.507 MeV and 0.573 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The spot corresponding to the main peak of radioactivity in the chromatogram obtained with the test solution is similar
in position to the spot corresponding to 2-iodohippuric acid in the chromatogram obtained with
the reference solution.
TESTS
pH (2.2.3). The pH of the solution is 3.5 to 8.5.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). Determine the relative amounts of
iodine-125, tellurium-121 and other radionuclidic impurities present. No radionuclides with longer
half lives than iodine-125 are detected. For the determination of iodine-125, tellurium-121 and
other radionuclidic impurities, retain the solution to be examined for a sufficient time to allow the
radioactivity of iodine-123 to decrease to a level which permits the detection of radionuclidic
impurities. Record the gamma-ray spectrum and X-ray spectrum of the decayed material using a
suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125). Not
more than 0.35 per cent of the total radioactivity is due to radionuclides other than iodine-123.
The injection may be released for use before completion of the test.
Radiochemical purity Examine by thin-layer chromatography (2.2.27) as described in the
monograph on Radiopharmaceutical preparations (0125), using silica gel GF254 R as the coating
substance.
Test solution. Dissolve 1 g of potassium iodide R in 10 ml of water R, add 1 volume of this solution to
10 volumes of the injection to be examined and use within 10 min of mixing. If necessary, dilute
with the reference solution (carrier) to give a radioactive concentration sufficient for the detection
method, for example 3.7 MBq per millilitre.
Reference solution (carrier). Dissolve 40 mg of 2-iodohippuric acid R and 40 mg of 2-iodobenzoic acid R in
4 ml of 0.1M sodium hydroxide, add 10 mg of potassium iodide R and dilute to 10 ml with water R.
Apply separately to the plate 10 l of each solution. Develop over a path of 12 cm (about 75 min)
using a mixture of 1 volume of water R, 4 volumes of glacial acetic acid R, 20 volumes of butanol R
and 80 volumes of toluene R. Allow the plate to dry in air and examine in ultraviolet light at 254 nm.
The chromatogram obtained with the reference solution shows a spot corresponding to 2-iodohippuric acid and nearer to the solvent front a spot corresponding to 2-iodobenzoic acid. Iodide

70-62
ion remains near the starting-line. Determine the distribution of radioactivity using a suitable
detector. In the chromatogram obtained with the test solution, not less than 96 per cent of the total
radioactivity is found in the spot corresponding to 2-iodohippuric acid and not more than 2 per
cent of the total radioactivity is found in either of the spots corresponding to 2-iodobenzoic acid
and to iodide ion.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised iodine-123 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
Store protected from light, in a cool place, in the conditions prescribed in the monograph on
Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).

70-63
The label states whether or not the preparation is suitable for renal plasma-flow studies.
_______________________________________________________________________________________________________________________ Ph Eur

Sodium Iodohippurate[131I] Injection


Sodium Iodohippurate[131I] Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0282]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Sodium iodohippurate (131I) injection is a sterile solution of sodium 2-(2-[131I]iodobenzamido)acetate. It may contain a suitable buffer and a suitable antimicrobial preservative such as benzyl
alcohol. Iodine-131 is a radioactive isotope of iodine and may be obtained by neutron irradiation of
tellurium or by extraction from uranium fission products. The injection contains not less than
90.0 per cent and not more than 110.0 per cent of the declared iodine-131 radioactivity at the date
and hour stated on the label. Not less than 96 per cent of the iodine-131 is in the form of sodium
2-iodohippurate. The specific radioactivity is 0.74 GBq to 7.4 GBq of iodine-131 per gram of
sodium 2-iodohippurate.
CHARACTERS
A clear, colourless liquid.
Iodine-131 has a half-life of 8.04 days and emits beta and gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised iodine-131 solution. Standardised iodine-131 solutions are available from laboratories
recognised by the competent authority. The most prominent gamma photon of iodine-131 has an
energy of 0.365 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The main peak of
radioactivity in the chromatogram obtained with the test solution is similar in position to the spot
corresponding to 2-iodohippuric acid in the chromatogram obtained with the reference solution.
TESTS
pH (2.2.3). The pH of the injection is 6.0 to 8.5.
Radionuclidic purity Record the gamma-ray spectrum using a suitable instrument as described in
the monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ
significantly from that of a standardised iodine-131 solution. Determine the relative amounts of
iodine-131, iodine-133, iodine-135 and other radionuclidic impurities present. Iodine-133 has a
half-life of 20.8 h and its most prominent gamma photons have energies of 0.530 MeV and
0.875 MeV. Iodine-135 has a half-life of 6.55 h and its most prominent gamma photons have
energies of 0.527 MeV, 1.132 MeV and 1.260 MeV. Not less than 99.9 per cent of the total radioactivity is due to iodine-131.
Radiochemical purity Examine by thin-layer chromatography (2.2.27) as described in the
monograph on Radiopharmaceutical preparations (0125), using silica gel GF254 R as the coating
substance.
Test solution. Dissolve 1 g of potassium iodide R in 10 ml of water R, add 1 volume of this solution to
10 volumes of the injection to be examined and use within 10 min of mixing. If necessary dilute
with the reference solution (carrier) to give a radioactive concentration sufficient for the detection
method, for example 3.7 MBq per millilitre.
Reference solution (carrier). Dissolve 40 mg of 2-iodohippuric acid R and 40 mg of 2-iodobenzoic acid R in
4 ml of 0.1M sodium hydroxide, add 10 mg of potassium iodide R and dilute to 10 ml with water R.
Apply separately to the plate 10 l of each solution. Develop over a path of 12 cm (about 75 min)
using a mixture of 1 volume of water R, 4 volumes of glacial acetic acid R, 20 volumes of butanol R
and 80 volumes of toluene R. Allow the plate to dry in air and examine in ultraviolet light at 254 nm.
The chromatogram obtained with the reference solution shows a spot corresponding to 2-iodohippuric acid and nearer to the solvent front a spot corresponding to 2-iodobenzoic acid. Iodide
ion remains near the starting-line. Determine the distribution of radioactivity using a suitable
detector. In the chromatogram obtained with the test solution, not less than 96 per cent of the total
radioactivity is found in the spot corresponding to 2-iodohippuric acid and not more than 2 per
cent of the total radioactivity is found in either of the spots corresponding to 2-iodobenzoic acid

70-64
and to iodide ion.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised iodine-131 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
Store protected from light, in a cool place, in the conditions prescribed in the monograph on
Radiopharmaceutical preparations (0125).

70-65
LABELLING
See Radiopharmaceutical preparations (0125).
The label states that the preparation is not necessarily suitable for renal plasma-flow studies.
_______________________________________________________________________________________________________________________ Ph Eur

Sodium Pertechnetate[99mTc] Injection (Fission)


Sodium Pertechnetate[99mTc] Injection (Fission) complies with the requirements of the 3rd edition of the
European Pharmacopoeia [0124]. These requirements are reproduced below.
Ph Eur ___________________________________________________________________________________________________________

This monograph applies to sodium pertechnetate (99mTc) injection obtained from molybdenum-99 extracted
from fission products of uranium. Sodium pertechnetate (99mTc) injection obtained from molybdenum-99
produced by the neutron irradiation of molybdenum is described in the monograph on Sodium Pertechnetate
(99mTc) Injection (Non-fission) (283).
DEFINITION
Sodium pertechnetate (99mTc) injection (fission) is a sterile solution containing technetium-99m in
the form of pertechnetate ion and made isotonic by the addition of sodium chloride. Technetium99m is a radionuclide formed by the decay of molybdenum-99. Molybdenum-99 is a radioactive
isotope of molybdenum extracted from uranium fission products. The injection contains not less
than 90.0 per cent and not more than 110.0 per cent of the declared technetium-99m radioactivity
at the date and hour stated on the label. Not less than 95 per cent of the radioactivity corresponds
to technetium-99m in the form of pertechnetate ion.
The radioactivity due to radionuclides other than technetium-99m, apart from that due to
technetium-99 resulting from the decay of technetium-99m, is not greater than that shown below,
expressed as a percentage of the total radioactivity and calculated with reference to the date and
hour of administration.
molybdenum-99
0.1 per cent
iodine-131
5 103 per cent
ruthenium-103
5 103 per cent
strontium-89
6 105 per cent
strontium-90
6 106 per cent
alpha-emitting impurities
1 107 per cent
other gamma-emitting impurities 0.01 per cent
The injection may be prepared from a sterile preparation of molybdenum-99 under aseptic
conditions.
CHARACTERS
A clear, colourless solution.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by measurement in an
instrument calibrated with the aid of such a solution. Standardised technetium-99m, molybdenum99, iodine-131, ruthenium-103, strontium-89 and strontium/yttrium-90 solutions are available
from laboratories recognised by the competent authority. The most prominent gamma photon of
technetium-99m has an energy of 0.140 MeV.
TESTS
pH (2.2.3). The pH of the injection is 4.0 to 8.0.
Radionuclidic purity Operate as described in the monograph on Radiopharmaceutical preparations
(0125).
Preliminary test. To obtain an approximate estimate before use of the injection, take a volume equivalent to 37 MBq and determine the gamma-ray spectrum using a sodium iodide detector with a
shield of lead, of thickness 6 mm, interposed between the sample and the detector. The response in
the region corresponding to the 0.740 MeV photon of molybdenum-99 does not exceed that
obtained using 37 kBq of a standardised molybdenum-99 solution measured under the same

70-66
conditions, when all measurements are expressed with reference to the date and hour of
administration.
Definitive test. Retain a sample of the injection for a sufficient time to allow the technetium-99m
radioactivity to decay to a sufficiently low level to permit the detection of radionuclidic impurities.
All measurements of radioactivity are expressed with reference to the date and hour of
administration.
Molybdenum-99. Record the gamma-ray spectrum of the decayed material in a suitable
instrument calibrated with the aid of a standardised molybdenum-99 solution. The most
prominent photons have energies of 0.181 MeV, 0.740 MeV and 0.778 MeV. Molybdenum-99
has a half-life of 66.0 h. Not more than 0.1 per cent of the total radioactivity is due to
molybdenum-99.
Iodine-131. Record the gamma-ray spectrum of the decayed material in a suitable instrument
calibrated with the aid of a standardised iodine-131 solution. The most prominent photon has
an energy of 0.365 MeV. Iodine-131 has a half-life of 8.04 days. Not more than 5 103 per
cent of the total radioactivity is due to iodine-131.
Ruthenium-103. Record the gamma-ray spectrum of the decayed material in a suitable
instrument calibrated using a standardised ruthenium-103 solution. The most prominent
photon has an energy of 0.497 MeV. Ruthenium-103 has a half-life of 39.3 days. Not more
than 5 103 per cent of the total radioactivity is due to ruthenium-103.
Strontium-89. Determine the presence of strontium-89 in the decayed material with an
instrument suitable for the detection of beta rays, by comparison with a standardised strontium89 solution. It is usually necessary first to carry out chemical separation of the strontium so that
the standard and the sample may be compared in the same physical and chemical form.
Strontium-89 decays with a beta emission of 1.492 MeV maximum energy and has a half-life of
50.5 days. Not more than 6 105 per cent of the total radioactivity is due to strontium-89.
Strontium-90. Determine the presence of strontium-90 in the decayed material with an
instrument suitable for the detection of beta rays. To distinguish strontium-90 from strontium89, compare the radioactivity of yttrium-90, the daughter nuclide of strontium-90, with an
yttrium-90 standard after the chemical separation of the yttrium. If prior chemical separation of
the strontium is necessary, the conditions of radioactive equilibrium must be ensured. The
yttrium-90 standard and the sample must be compared in the same physical and chemical form.
Strontium-90 and yttrium-90 decay with respective beta emissions of 0.546 MeV and
2.284 MeV maximum energy and half-lives of 29.1 years and 64.0 h. Not more than 6 106
per cent of the total radioactivity is due to strontium-90.
Other gamma-emitting impurities. Examine the gamma-ray spectrum of the decayed material for
the presence of other radionuclidic impurities, which should, where possible, be identified and
quantified. The total gamma radioactivity due to these impurities does not exceed 0.01 per cent
of the total radioactivity.
Alpha-emitting impurities. Measure the alpha radio-activity of the decayed material to detect any
alpha-emitting radionuclidic impurities, which should, where possible, be identified and
quantified. The total alpha radio-activity due to these impurities does not exceed 1 107 per
cent of the total radioactivity.
Radiochemical purity Examine by descending paper chromatography (2.2.26), as described in
the monograph on Radiopharmaceutical preparations (0125).
Test solution. Dilute the preparation to be examined with water R to a suitable radioactive concentration.
Apply 5 l of the test solution. Develop for 2 h using a mixture of 20 volumes of water R and 80
volumes of methanol R. Allow the paper to dry. Determine the distribution of radioactivity using a
suitable detector. Not less than 95 per cent of the total radioactivity is in the spot corresponding
to pertechnetate ion, which has an Rf value of about 0.6.
Aluminium In a test tube about 12 mm in internal diameter, mix 1 ml of acetate buffer solution pH
4.6 R and 2 ml of a 1 in 2.5 dilution of the injection in water R. Add 0.05 ml of a 10 g/l solution of
chromazurol S R. After 3 min, the colour of the solution is not more intense than that of a standard
prepared at the same time and in the same manner using 2 ml of aluminium standard solution (2 ppm
Al) R (5 ppm).
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.

70-67
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
_______________________________________________________________________________________________________________________ Ph Eur

Sodium Pertechnetate[99mTc] Injection (Non-fission)


Sodium Pertechnetate[99mTc] Injection (Non-fission) complies with the requirements of the 3rd edition of the
European Pharmacopoeia [0283]. These requirements are reproduced below.
Ph Eur ___________________________________________________________________________________________________________

This monograph applies to sodium pertechnetate (99mTc) injection obtained from molybdenum-99 produced by
neutron irradiation of molybdenum. Sodium pertechnetate (99mTc) injection obtained from molybdenum-99
extracted from fission products of uranium is described in the monograph on Sodium Pertechnetate(99mTc)
Injection (Fission) (124).
DEFINITION
Sodium pertechnetate (99mTc) injection (non-fission) is a sterile solution containing technetium99m in the form of pertechnetate ion and made isotonic by the addition of sodium chloride.
Technetium-99m is a radionuclide formed by the decay of molybdenum-99. Molybdenum-99 is a
radioactive isotope of molybdenum produced by neutron irradiation of molybdenum. The injection
contains not less than 90.0 per cent and not more than 110.0 per cent of the declared technetium99m radioactivity at the date and hour stated on the label. Not less than 95 per cent of the radioactivity corresponds to technetium-99m in the form of pertechnetate ion.
The radioactivity due to radionuclides other than technetium-99m, apart from that due to
technetium-99 resulting from the decay of technetium-99m is not greater than that shown below,
expressed as a percentage of the total radioactivity and calculated with reference to the date and
hour of administration.
Molybdenum-99
0.1 per cent
Other radionuclidic impurities 0.01 per cent
The injection may be prepared from a sterile preparation of molybdenum-99 under aseptic
conditions.
CHARACTERS
A clear, colourless solution.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the injection is 4.0 to 8.0.
Radionuclidic purity Operate as described in the monograph on Radiopharmaceutical preparations
(0125).
Preliminary test. To obtain an approximate estimate before use of the injection, take a volume equivalent to 37 MBq and record the gamma-ray spectrum using a sodium iodide detector with a shield
of lead, of thickness 6 mm, interposed between the sample and the detector. The response in the
region corresponding to the 0.740 MeV photon of molybdenum-99 does not exceed that obtained
using 37 kBq of a standardised solution of molybdenum-99 measured under the same conditions,
when all measurements are expressed with reference to the date and hour of administration.
Definitive test. Retain a sample of the injection for a sufficient time to allow the technetium-99m
radioactivity to decay to a sufficiently low level to permit the detection of radionuclidic impurities.
All measurements of radioactivity are expressed with reference to the date and hour of

70-68
administration.
Molybdenum-99. Record the gamma-ray spectrum of the decayed material in a suitable
instrument calibrated using a standardised molybdenum-99 solution. The most prominent
gamma photons have energies of 0.181 MeV, 0.740 MeV and 0.778 MeV. Molybdenum-99
has a half-life of 66.0 h. Not more than 0.1 per cent of the total radioactivity is due to
molybdenum-99.
Other gamma-emitting impurities. Examine the gamma-ray spectrum of the decayed material for
the presence of other radionuclidic impurities, which should, where possible, be identified and
quantified. The total radioactivity due to other radionuclidic impurities does not exceed
0.01 per cent of the total radioactivity.
Radiochemical purity Examine by descending paper chromatography (2.2.26), as described in
the monograph on Radiopharmaceutical preparations (0125).
Test solution. Dilute the injection with water R to a suitable radioactive concentration.
Apply 5 l of the test solution. Develop for 2 h using a mixture of 20 volumes of water R and 80
volumes of methanol R. Allow the paper to dry in air. Determine the distribution of radioactivity
using a suitable detector. Not less than 95 per cent of the total radioactivity is found in the spot
corresponding to pertechnetate ion, which has an Rf value of about 0.6.
Aluminium In a test tube about 12 mm in internal diameter, mix 1 ml of acetate buffer solution pH
4.6 R and 2 ml of a 1 in 2.5 dilution of the injection in water R. Add 0.05 ml of a 10 g/l solution of
chromazurol S R. After 3 min, the colour of the solution is not more intense than that of a standard
prepared at the same time in the same manner using 2 ml of aluminium standard solution (2 ppm Al) R
(5 ppm).
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY

70-69
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
_______________________________________________________________________________________________________________________ Ph Eur

Sodium Phosphate[32P] Injection


Sodium Phosphate[32P] Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0284]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Sodium phosphate (32P) injection is a sterile solution of disodium and monosodium (32P)
orthophosphates made isotonic by the addition of sodium chloride. Phosphorus-32 is a radioactive
isotope of phosphorus and may be produced by neutron irradiation of sulphur. The injection
contains not less than 90.0 per cent and not more than 110.0 per cent of the declared phosphorus32 radioactivity at the date and hour stated on the label. Not less than 95 per cent of the radioactivity corresponds to phosphorus-32 in the form of orthophosphate ion. The specific radioactivity is not less than 11.1 MBq of phosphorus-32 per milligram of orthophosphate ion.
CHARACTERS
A clear, colourless solution.
Phosphorus-32 has a half-life of 14.3 days and emits beta radiation.
IDENTIFICATION
A. Record the beta-ray spectrum or the beta-ray absorption curve using a suitable method as
described in the monograph on Radiopharmaceutical preparations (0125). The spectrum or curve does
not differ significantly from that of a standardised phosphorus-32 solution obtained under the same
conditions. Standardised phosphorus-32 solutions are available from laboratories recognised by
the competent authority. The maximum energy of the beta radiation is 1.71 MeV.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the injection is 6.0 to 8.0.
Radionuclidic purity Record the beta-ray spectrum or the beta-ray absorption curve using a
suitable method as described in the monograph on Radiopharmaceutical preparations (0125). The
spectrum or curve does not differ significantly from that of a standardised phosphorus-32 solution
obtained under the same conditions.
Radiochemical purity Examine by ascending paper chromatography (2.2.26), as described in the
monograph on Radiopharmaceutical preparations (0125).
Test solution. Dilute the injection with water R until the radioactivity is equivalent to 10,000 to
20,000 counts per minute per 10 l.
Reference solution. Prepare a solution of phosphoric acid R containing 2 mg of phosphorus per
millilitre.
Using a strip of paper 25 mm wide and about 300 mm long, apply 10 l of the reference solution.
Apply to the same starting-point 10 l of the test solution. Develop for 16 h using a mixture of
0.3 ml of ammonia R, 5 g of trichloroacetic acid R, 25 ml of water R and 75 ml of 2-propanol R. Allow
the paper to dry in air. Determine the position of the inactive phosphoric acid by spraying with a
50 g/l solution of perchloric acid R and then with a 10 g/l solution of ammonium molybdate R. Expose
the paper to hydrogen sulphide R. A blue colour develops. Determine the position of the radioactive
spot by autoradiography or by measuring the radioactivity over the whole length of the chromatogram. Not less than 95 per cent of the total radioactivity of the chromatogram is found in the spot
corresponding to phosphoric acid.
Phosphates Dilute the injection with water R to give a radioactive concentration of 370 kBq of
phosphorus-32 per millilitre. Mix in a volumetric flask, with shaking, 1.0 ml of the solution with a

70-70
mixture of 0.5 ml of a 2.5 g/l solution of ammonium vanadate R, 0.5 ml of ammonium molybdate
solution R and 1 ml of perchloric acid R and dilute to 5.0 ml with water R. After 30 min, the solution is
not more intensely coloured than a standard prepared at the same time in the same manner using
1.0 ml of a solution containing 33 mg of orthophosphate ion per litre.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical

70-71
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised phosphorus-32 solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
_______________________________________________________________________________________________________________________ Ph Eur

Strontium[89Sr] Chloride Injection


Strontium[89Sr] Chloride Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [1475]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Strontium(89Sr) chloride injection is a sterile solution of [89Sr]strontium chloride. Strontium-89 is a
radioactive isotope of strontium and is produced by neutron irradiation of strontium enriched in
strontium-88. The injection contains not less than 90.0 per cent and not more than 110.0 per cent
of the declared strontium-89 radioactivity at the date stated on the label. Not more than 0.6 per
cent of the total radioactivity is due to radionuclides other than strontium-89. The specific radioactivity is not less than 1.8 MBq of strontium-89 per milligram of strontium. The injection contains
6.0 mg/ml to 12.5 mg/ml of strontium.
CHARACTERS
A clear, colourless solution.
Strontium-89 has a half-life of 50.5 days and emits beta radiation with a maximum energy of
1.492 MeV.
IDENTIFICATION
A. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised strontium-89 solution, when measured either by direct comparison or
by using an instrument calibrated with the aid of such a solution. Standardised strontium-89
solutions are available from laboratories recognised by the competent authority. The gamma
photon detected has an energy of 0.909 MeV and is due to the short-lived daughter product,
yttrium-89m (formed in 0.01 per cent of the disintegrations), in equilibrium with the strontium-89.
B. To 0.1 ml of the injection to be examined, add 1 ml of a freshly prepared 1 g/l solution of sodium
rhodizonate R. Mix and allow to stand for 1 min. A reddish-brown precipitate is formed.
C. To 0.1 ml of silver nitrate solution R2 add 50 l of the injection to be examined. A white precipitate
is formed.
TESTS
pH (2.2.3). The pH of the solution is 4.0 to 7.5.
Radionuclidic purity
a. Gamma emitters Record the gamma-ray and X-ray spectrum of the injection to be examined using
a suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125). Not
more than 0.4 per cent of the total radioactivity in the preparation to be examined is due to gamma
emitting radionuclides other than yttrium-89m.
b. Beta emitters Evaporate to dryness 100 l of the injection to be examined under a radiant heat
source. Dissolve the residue in 2 ml of 47 per cent hydrobromic acid R, evaporate to dryness under the
radiant heat source and dissolve the residue in 2 ml of dilute hydrobromic acid R1. Transfer the
solution to the top of a column, 5 mm to 6 mm in diameter, packed with approximately 2 ml of
cationic exchange resin R1 (100 m to 250 m), previously conditioned with dilute hydrobromic acid R1
and elute the column with the same solvent until 10 ml of eluate has been collected into a container
containing 50 l of a 15 g/l solution of anhydrous sodium sulphate R in 1M hydrochloric acid.

70-72
To a liquid scintillation vial add an appropriate volume of scintillation liquid followed by 1 ml of
water R, 0.1 ml of a 15 g/l solution of anhydrous sodium sulphate R in 1M hydrochloric acid and 100 l of
eluate. Shake to obtain a clear solution. Using suitable counting equipment as described in the
monograph on Radiopharmaceutical preparations (0125), determine the radioactivity due to sulphur35 and phosphorus-32 in the sample.
Taking into account the recovery efficiency of the separation, counting efficiency and radioactive
decay, determine the radioactive concentration of sulphur-35 and phosphorus-32 in the sample
and hence the percentage of total beta emitting impurities in the injection to be examined. Not
more than 0.2 per cent of the total radioactivity in the injection to be examined is due to the sum of
sulphur-35 and phosphorus-32 radioactivities.
Note: The following tests for aluminium, iron and lead may be carried out simultaneously with the test
strontium. If this is not the case, the reference solutions are prepared such that they contain strontium at
approximately the same concentration as in the test solution.
Aluminium Not more than 2 g/ml, determined by atomic emission spectrometry (plasma or arc
method) (Method I, 2.2.22).
Test solution. Dilute 0.2 ml of the injection to be examined to a suitable volume with dilute nitric
acid R.
Reference solutions. Prepare the reference solutions using aluminium standard solution (10 ppm Al) R
diluted as necessary with dilute nitric acid R.
Iron Not more than 5 g/ml, determined by atomic emission spectrometry (plasma or arc method)
(Method I, 2.2.22).
Test solution. Dilute 0.2 ml of the injection to be examined to a suitable volume with dilute nitric
acid R.
Reference solutions. Prepare the reference solutions using iron standard solution (20 ppm Fe) R diluted
as necessary with dilute nitric acid R.
Lead Not more than 5 g/ml, determined by atomic emission spectrometry (plasma or arc method)
(Method I, 2.2.22).
Test solution. Dilute 0.2 ml of the injection to be examined to a suitable volume with dilute nitric
acid R.
Reference solutions. Prepare the reference solutions using lead standard solution (10 ppm Pb) R diluted
as necessary with dilute nitric acid R.
Strontium 6.0 mg/ml to 12.5 mg/ml. Examine by atomic emission spectrometry (Method I, 2.2.22).
Test solution. Dilute 0.2 ml of the injection to be examined to a suitable volume with dilute nitric
acid R.
Reference solutions. Prepare the reference solutions using strontium standard solution (1.0 per cent Sr) R
diluted as necessary with dilute nitric acid R.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical

70-73
preparations (0125).
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable equipment by comparison with a standardised strontium-89 solution or by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Albumin Injection


Technetium[99mTc] Albumin Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia for Technetium[99mTc] Human Albumin Injection [0640]. These requirements are
reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) human albumin injection is a sterile, apyrogenic solution of human albumin
labelled with technetium-99m. It contains a reducing substance, such as a tin salt in an amount not
exceeding 1 mg of Sn per millilitre; it may contain a suitable buffer and an antimicrobial
preservative. Although, at present, no definite value for a maximum limit of tin can be fixed,
available evidence tends to suggest the importance of keeping the ratio of tin to albumin as low as
possible. The human albumin used complies with the requirements of the monograph on Human
albumin solution (0255). The injection contains not less than 90.0 per cent and not more than
110.0 per cent of the declared technetium-99m radioactivity at the date and hour stated on the
label. The injection contains not less than 90.0 per cent and not more than 110.0 per cent of the
quantity of albumin stated on the label. Not less than 80 per cent of the radioactivity is associated
with the albumin fractions II to V. Not more than 5.0 per cent of the radioactivity due to
technetium-99m corresponds to free pertechnetate, as determined by the method described in the
test for radiochemical purity.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable
sterile and apyrogenic ingredients and calculating the ratio of radionuclidic impurities with
reference to the date and hour of administration.
CHARACTERS
A clear, colourless or pale-yellow solution.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. Using a suitable range of species-specific antisera, carry out precipitation tests on the
preparation to be examined. The test is to be carried out using antisera specific to the plasma
proteins of each species of domestic animal currently used in the preparation of materials of
biological origin in the country concerned. The injection is shown to contain proteins of human
origin and gives negative results with antisera specific to plasma proteins of other species.
C. Examine by a suitable immunoelectrophoresis technique. Using antiserum to normal human
serum, compare normal human serum and the injection to be examined, both diluted if necessary.
The main component of the injection to be examined corresponds to the main component of the
normal human serum. The diluted solution may show the presence of small quantities of other
plasma proteins.
TESTS
pH (2.2.3). The pH of the injection is 2.0 to 6.5.

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Radiochemical purity
(a) Examine by thin-layer chromatography (2.2.27) as described in the monograph on Radiopharmaceutical preparations (0125), using silica gel as the coating substance on a glass-fibre sheet.
Heat the plate at 110C for 10 min. Use a plate such that during development the mobile phase
migrates over a distance of 10 cm to 15 cm in about 10 min.
Apply to the plate 5 l to 10 l of the injection to be examined and allow to dry. Develop over a
path of 10 cm to 15 cm using methyl ethyl ketone R. Allow the plate to dry. Determine the
distribution of radioactivity using a suitable detector. The technetium-99m human albumin
complex remains at the starting-point and pertechnetate ion migrates near to the solvent front. Not
more than 5.0 per cent of the technetium-99m radioactivity corresponds to technetium in the form
of pertechnetate ion.
(b) Examine by size-exclusion chromatography (2.2.30).
Mobile phase (concentrated). Dissolve 1.124 g of potassium dihydrogen phosphate R, 4.210 g of disodium
hydrogen phosphate R, 1.17 g of sodium chloride R and 0.10 g of sodium azide R in 100 ml of water R.
Test solution. Mix 0.25 ml of the injection to be examined with 0.25 ml of the mobile phase
(concentrated). Use immediately after dilution.
The chromatographic procedure may be carried out using:
a stainless steel column 0.6 m long and 7.5 mm in internal diameter, packed with silica gel for
size-exclusion chromatography R,
as the mobile phase at a flow rate of 0.6 ml per minute a mixture of equal volumes of mobile
phase (concentrated) and water R,
a radioactivity detector set for technetium-99m,
a loop injector.
Inject 200 l of the test solution. Continue the chromatography for at least 10 min after
background level is reached.
Peaks are eluted with the following retention times:
I High molecular mass compound
1920 min
II Poly III-albumin
2324 min
III Poly II-albumin
2527 min
IV Poly I-albumin
2829 min
V Human serum albumin
3233 min
VI Tin colloid
4047 min
VII Pertechnetate
48 min
At least 80 per cent of the radioactivity applied to the column is associated with the albumin
fractions II to V.
Albumin
Reference solution. Dilute human albumin solution R with a 9 g/l solution of sodium chloride R to a concentration of 5 mg of albumin per millilitre.
To 1.0 ml of the injection to be examined and to 1.0 ml of the reference solution add 4.0 ml of
biuret reagent R and mix. After exactly 30 min, measure the absorbance (2.2.25) of each solution at
540 nm, using as the compensation liquid a 9 g/l solution of sodium chloride R treated in the same
manner. From the absorbances measured, calculate the content of albumin in the injection to be
examined in milligrams per millilitre.
Tin
Test solution. To 1.0 ml of the injection to be examined add 1.0 ml of 2M hydrochloric acid. Heat in a
water-bath at 100C for 30 min. Cool and centrifuge at 300 g for 10 min. Dilute 1.0 ml of the
supernatant liquid to 10 ml with 1M hydrochloric acid.
Reference solution. Dissolve 95 mg of stannous chloride R in 1M hydrochloric acid and dilute to 1000.0 ml
with the same acid.
To 1.0 ml of each solution add 0.4 ml of a 20 g/l solution of sodium lauryl sulphate R, 0.05 ml of
thioglycollic acid R, 0.1 ml of dithiol reagent R and 3.0 ml of 0.2M hydrochloric acid. Mix. Measure the
absorbance (2.2.25) of each solution at 540 nm, using 0.2M hydrochloric acid as the compensation
liquid. The absorbance of the test solution is not greater than that of the reference solution (1 mg
of Sn per millilitre).
Physiological distribution Inject a volume not greater than 0.5 ml and containing not more than
1.0 mg of albumin into a suitable vein such as a caudal vein or a saphenous vein of each of three
male rats, each weighing 150 g to 250 g. Measure the radioactivity in the syringe before and after
the injection. Kill the rats 30 min after the injection. Take one millilitre of blood by a suitable
method and remove the liver and, if a caudal vein has been used for the injection, the tail. Using a
suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125) deter-

70-75
mine the radioactivity in 1 ml of blood, in the liver and, if a caudal vein has been used for the
injection, in the tail. Determine the percentage of radioactivity in the liver and in 1 ml of blood with
respect to the total radioactivity calculated as the difference between the measurements made on
the syringe minus the activity in the tail (if a caudal vein has been used for the injection). Correct
the blood concentration by multiplying by a factor of m/200 where m is the body mass of the rat in
grams. In not fewer than two of the three rats used, the radioactivity in the liver is not more than
15 per cent and that in blood, after correction, is not less than 3.5 per cent.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Bacterial endotoxins (2.6.14). Not more than 175/V I.U. of endotoxin per millilitre, V being the

70-76
maximum recommended dose in millilitres.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
The label states:
the amount of albumin,
the amount of tin, if any.
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Colloidal Rhenium Sulphide Injection


Technetium[99mTc] Colloidal Rhenium Sulphide Injection complies with the requirements of the 3rd edition
of the European Pharmacopoeia [0126]. These requirements are reproduced after the heading Definition
below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) colloidal rhenium sulphide injection is a sterile, apyrogenic colloidal dispersion
of rhenium sulphide the micelles of which are labelled with technetium-99m. It is stabilised with
gelatin. The injection contains not less than 90.0 per cent and not more than 110.0 per cent of the
declared technetium-99m radioactivity at the date and hour stated on the label. Not less than
92 per cent of the radioactivity corresponds to technetium-99m in colloidal form. The pH of the
injection may be adjusted by the addition of a suitable buffer such as a citrate buffer solution. The
injection contains a variable amount of colloidal rhenium sulphide, not exceeding 0.22 mg of
rhenium (Re) per millilitre, according to the method of preparation.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable
sterile, apyrogenic ingredients and calculating the ratio of radionuclidic impurities with reference to
the date and hour of administration.
CHARACTERS
A light-brown liquid.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the injection.
C. To 1 ml add 5 ml of hydrochloric acid R, 5 ml of a 50 g/l solution of thiourea R and 1 ml of a 200 g/l
solution of stannous chloride R in hydrochloric acid R. A yellow colour is produced.
TESTS
pH (2.2.3). The pH of the injection is 4.0 to 7.0.
Rhenium
Test solution. Use 1 ml of the injection to be examined.
Reference solutions. Using a solution containing 100 g of potassium perrhenate R (equivalent to
60 ppm of Re) and 240 g of sodium thiosulphate R per millilitre, prepare a suitable range of solutions
and dilute to the same final volume with water R.
To the test solution and to 1 ml of each of the reference solutions add 5 ml of hydrochloric acid R,
5 ml of a 50 g/l solution of thiourea R and 1 ml of a 200 g/l solution of stannous chloride R in hydro-

70-77
chloric acid R and dilute to 25.0 ml with water R. Allow to stand for 40 min and measure the
absorbance (2.2.25) of each solution at 400 nm, using a reagent blank as the compensation liquid.
Using the absorbances obtained with the reference solutions, draw a calibration curve and
calculate the concentration of rhenium in the injection to be examined.
Radiochemical purity Examine by ascending paper chromatography (2.2.26), as described in the
monograph on Radiopharmaceutical preparations (0125).
Apply to the paper 10 l of the injection. Develop immediately over a path of 10 cm to 15 cm
using a 9 g/l solution of sodium chloride R. Allow the paper to dry. Determine the distribution of
radioactivity using a suitable detector. Technetium-99m in colloidal form remains at the startingpoint and pertechnetate ion migrates with an Rf of about 0.6. There may be other impurities with
an Rf of 0.8 to 0.9. The radioactivity corresponding to technetium-99m in colloidal form
represents not less than 92 per cent of the total radioactivity of the chromatogram.
Physiological distribution Inject a volume not greater than 0.2 ml into the caudal vein of each of
three mice each weighing 20 g to 25 g. Sacrifice the mice 20 min after the injection, remove the
liver, spleen and lungs and measure the radioactivity in the organs using a suitable instrument as
described in the monograph on Radiopharmaceutical preparations (0125). Measure the radioactivity in
the rest of the body after having removed the tail. Determine the percentage of radioactivity in the
liver, the spleen and the lungs from the expression:
A
100
B
A = radioactivity of the organ concerned,
B = total radioactivity in the liver, the spleen, the lungs and the rest of the body.
In each of the three mice at least 80 per cent of the radioactivity is found in the liver and spleen and
not more than 5 per cent in the lungs. If the distribution of radioactivity in one of the three mice
does not correspond to the prescribed proportions, repeat the test on a further three mice. The
preparation complies with the test if the prescribed distribution of radioactivity is found in five of
the six mice used. The injection may be released for use before completion of the test.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.

70-78
Pyrogens It complies with the test for pyrogens prescribed in the monograph on Radiopharmaceutical preparations (0125). Inject not less than 0.1 ml per kilogram of the rabbits mass. The
injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
The label states, in particular, the quantity of rhenium per millilitre.
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Colloidal Sulphur Injection


Technetium[99mTc] Colloidal Sulphur Injection complies with the requirements of the 3rd edition of the
European Pharmacopoeia [0131]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) colloidal sulphur injection is a sterile, apyrogenic colloidal dispersion of
sulphur, the micelles of which are labelled with technetium-99m. It may be stabilised with a colloidprotecting substance based on gelatin. The injection contains not less than 90.0 per cent and not
more than 110.0 per cent of the declared technetium-99m radioactivity at the date and hour stated
on the label. Not less than 92 per cent of the radioactivity corresponds to technetium-99m in
colloidal form. The pH of the injection may be adjusted by the addition of a suitable buffer, such as
an acetate, citrate or phosphate buffer solution. The injection contains a variable amount of
colloidal sulphur, according to the method of preparation.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable
sterile, apyrogenic ingredients and calculating the ratio of radionuclidic impurities with reference to
the date and hour of administration.
CHARACTERS
A clear to opalescent, colourless to yellowish liquid.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the injection.
C. In a test-tube 100 mm long and 16 mm in internal diameter, evaporate 0.2 ml of the injection to
dryness. Dissolve the sulphur by shaking the residue with 0.2 ml of pyridine R and add about 20 mg
of benzoin R. Cover the open end of the tube with a filter paper moistened with lead acetate
solution R. Heat the test-tube in a bath containing glycerol at 150C. The paper slowly becomes
brown.
TESTS
pH (2.2.3). The pH of the injection is 4.0 to 7.0.
Radiochemical purity Examine by ascending paper chromatography (2.2.26), as described in the
monograph on Radiopharmaceutical preparations (0125).
Apply to the paper 10 l of the injection. Develop immediately over a path of 10 cm to 15 cm
with a 9 g/l solution of sodium chloride R. Allow the paper to dry. Determine the distribution of
radioactivity using a suitable detector. Technetium-99m in colloidal form remains at the starting-

70-79
point and pertechnetate ion migrates with an Rf of 0.6. There may be other impurities of Rf 0.8 to
0.9. The radioactivity corresponding to technetium-99m in colloidal form represents not less than
92 per cent of the total radioactivity of the chromatogram.
Physiological distribution Inject a volume not greater than 0.2 ml into the caudal vein of each of
three mice, each weighing 20 g to 25 g. Sacrifice the mice 20 min after the injection, remove the
liver, spleen and lungs and measure the radioactivity in the organs using a suitable instrument as
described in the monograph on Radiopharmaceutical preparations (0125). Measure the radioactivity in
the rest of the body after having removed the tail. Determine the percentage of radioactivity in the
liver, the spleen and the lungs from the expression:
A
100
B
A = radioactivity of the organ concerned,
B = total radioactivity in the liver, the spleen, the lungs and the rest of the body.
In each of the three mice at least 80 per cent of the radioactivity is found in the liver and spleen and
not more than 5 per cent in the lungs. If the distribution of radioactivity in one of the three mice
does not correspond to the prescribed proportions, repeat the test on a further three mice. The
preparation complies with the test if the prescribed distribution of radioactivity is found in five of
the six mice used. The injection may be released for use before completion of the test.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical

70-80
preparations (0125). The injection may be released for use before completion of the test.
Pyrogens It complies with the test for pyrogens prescribed in the monograph on Radiopharmaceutical preparations (0125). Inject not less than 0.1 ml per kilogram of the rabbits mass. The
injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Colloidal Tin Injection


Technetium[99mTc] Colloidal Tin Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0689]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) colloidal tin injection is a sterile, colloidal dispersion of tin labelled with
technetium-99m. The injection contains a variable quantity of tin not exceeding 1 mg of Sn per
millilitre; it contains fluoride ions, it may be stabilised with a suitable, apyrogenic colloid-protecting
substance and it may contain a suitable buffer. The injection contains not less than 90.0 per cent
and not more than 110.0 per cent of the declared technetium-99m radioactivity at the date and
hour stated on the label. Not less than 95 per cent of the radioactivity corresponds to technetium99m in colloidal form.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable
sterile ingredients and calculating the ratio of radionuclidic impurities with reference to the date
and hour of administration. Syringes for handling the eluate intended for labelling of the final
product, or the final product, should not contain rubber parts.
CHARACTERS
A clear or opalescent, colourless liquid.
Technetium-99m has a half life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. Mix 0.05 ml of zirconyl nitrate solution R with 0.05 ml of alizarin S solution R. Add 0.05 ml of the
injection to be examined. A yellow colour is produced.
TESTS
pH (2.2.3). The pH of the injection to be examined is 4.0 to 7.0.
Radiochemical purity Examine by thin-layer chromatography (2.2.27) as described in the monograph on Radiopharmaceutical preparations (0125), using silica gel as the coating substance on a glassfibre sheet. Heat the plate at 110C for 10 min. Use a plate such that during development the
mobile phase migrates over a distance of 10 cm to 15 cm in about 10 min.
Apply to the plate 5 l to 10 l of the injection to be examined. Develop immediately over a path
of 10 cm to 15 cm using a 9 g/l solution of sodium chloride R purged with nitrogen R. Allow the plate to
dry. Determine the distribution of radioactivity using a suitable detector. Technetium-99m in
colloidal form remains at the starting point and pertechnetate ion migrates near to the solvent
front. Not less than 95 per cent of the technetium-99m radioactivity corresponds to technetium in

70-81
colloidal form.
Tin
Test solution. Dilute 3.0 ml of the injection to be examined to 50.0 ml with 1M hydrochloric acid.
Reference solution. Dissolve 0.115 g of stannous chloride R in 1M hydrochloric acid and dilute to
1000.0 ml with the same acid.
To 1.0 ml of each solution add 0.4 ml of a 20 g/l solution of sodium lauryl sulphate R, 0.05 ml of
thioglycollic acid R, 0.1 ml of dithiol reagent R and 3.0 ml of 0.2M hydrochloric acid. Mix. Measure the
absorbance (2.2.25) of each solution at 540 nm, using 0.2M hydrochloric acid as the compensation
liquid. The absorbance of the test solution is not greater than that of the reference solution (1 mg
of Sn per millilitre).
Physiological distribution Inject not more than 0.2 ml into a caudal vein of each of three mice,
each weighing 20 g to 25 g. Kill the mice 20 min after the injection and remove the liver, spleen and
lungs. Measure the radioactivity in the organs using a suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125). Measure the radioactivity in the rest of the body,
after having removed the tail. Determine the percentage of radioactivity in the liver, the spleen and
the lungs with respect to the total radioactivity of all organs and the rest of the body excluding the
tail.
In each of the three mice at least 80 per cent of the radioactivity is found in the liver and spleen
and not more than 5 per cent in the lungs. If the distribution of radioactivity in one of the three
mice does not correspond to the prescribed proportions, repeat the test on a further three mice.

70-82
The preparation complies with the test if the prescribed distribution of radioactivity is found in five
of the six mice used.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Etifenin Injection


Technetium[99mTc] Etifenin Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0585]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) etifenin injection is a sterile solution which may be prepared by mixing
sodium pertechnetate (99mTc) injection (fission or non-fission) with solutions of etifenin [[(2,6diethylphenyl)carbamoylmethylimino]di-acetic acid; C16H22N2O5] and stannous chloride. The
injection contains a variable quantity of tin (Sn) not exceeding 0.2 mg per millilitre. The injection
contains not less than 90.0 per cent and not more than 110.0 per cent of the declared technetium99m radioactivity at the date and hour stated on the label. Not less than 95.0 per cent of the radioactivity corresponds to technetium-99m complexed with etifenin.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable,
sterile ingredients and calculating the ratio of radionuclidic impurities with reference to the date
and hour of administration.
CHARACTERS
A clear, colourless solution.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.l40 MeV.
B. Examine by liquid chromatography (2.2.29).
Test solution. Dilute the injection to be examined with methanol R to obtain a solution containing
about l mg of etifenin per millilitre.
Reference solution. Dissolve 5.0 mg of etifenin CRS in methanol R and dilute to 5.0 ml with the same
solvent.
The chromatographic procedure may be carried out using:
a column 0.25 m long and 4.6 mm in internal diameter packed with octadecylsilyl silica gel for
chromatography R (5 m to 10 m),
as mobile phase at a flow rate of 1 ml per minute a mixture of 20 volumes of methanol R and 80
volumes of a 14 g/l solution of potassium dihydrogen phosphate R adjusted to pH 2.5 by the
addition of phosphoric acid R,
a spectrophotometer set at 230 nm.
Inject 20 l of each solution. The principal peak in the chromatogram obtained with the test
solution has a similar retention time to the principal peak in the chromatogram obtained with the
reference solution.

70-83
TESTS
pH (2.2.3). The pH of the injection is 4.0 to 6.0.
Radiochemical purity Examine by thin-layer chromatography (2.2.27), as described in the monograph on Radiopharmaceutical preparations (0125), using silicic acid as the coating substance on a
glass-fibre sheet. Heat the plate at 110C for l0 min. The plate used should be such that during
development the mobile phase moves over a distance of 10 cm to 15 cm in about 15 min.
Apply to the plate 5 l to 10 l of the injection to be examined. Develop immediately over a path
of 10 cm to 15 cm using a 9 g/l solution of sodium chloride R. Allow the plate to dry. Determine the
distribution of radioactivity using a suitable detector. Technetium-99m complexed with etifenin
migrates almost to the middle of the chromatogram and pertechnetate ion migrates with the solvent
front. Impurities in colloidal form remain at the starting point. The radioactivity corresponding to
technetium-99m complexed with etifenin represents not less than 95.0 per cent of the total radioactivity of the chromatogram.
Physiological distribution Inject 0.1 ml (equivalent to about 3.7 MBq) into a caudal vein of each
of three mice, each weighing 20 g to 25 g. Kill the mice l h after the injection. Remove the liver,
gall-bladder, small intestine, large intestine and kidneys, collecting excreted urine. Measure the
radioactivity in the organs using a suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125). Measure the radioactivity of the rest of the body, after having
removed the tail. Determine the percentage of radioactivity in each organ from the expression:
A
100
B
A = radioactivity of the organ concerned,
B = radioactivity of all organs and the rest of the body, excluding the tail.
In not fewer than two mice the sum of the percentages of radioactivity in the gall-bladder and small
and large intestine is not less than 80 per cent. Not more than 3 per cent of the radioactivity is
present in the liver, and not more than 2 per cent in the kidneys.
Tin
Test solution. Dilute 1.0 ml of the injection to be examined to 5.0 ml with 1M hydrochloric acid.
Reference solution. Prepare a reference solution containing 0.075 mg of stannous chloride R per
millilitre in 1M hydrochloric acid.
To 1.0 ml of each solution add 0.4 ml of a 20 g/l solution of sodium lauryl sulphate R, 0.05 ml of

70-84
thioglycollic acid R, 0.l ml of dithiol reagent R and 3.0 ml of 0.2M hydrochloric acid. Mix. Measure the
absorbance (2.2.25) of each solution at 540 nm, using 0.2M hydrochloric acid as the compensation
liquid. The absorbance of the test solution is not greater than that of the reference solution (0.2 mg
of Sn per millilitre).
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Gluconate Injection


Technetium[99mTc] Gluconate Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [1047]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) gluconate injection is a sterile solution, which may be prepared by mixing
solutions of calcium gluconate and a stannous salt or other suitable reducing agent with
sodium pertechnetate (99mTc) injection (fission or non-fission). The injection contains not less than
90.0 per cent and not more than 110.0 per cent of the declared technetium-99m radioactivity at
the date and hour stated on the label. Not less than 90 per cent of the radioactivity corresponds to
technetium-99m gluconate complex.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable
sterile ingredients and calculating the ratio of radionuclidic impurities with reference to the date
and hour of administration.
CHARACTERS
A slightly opalescent solution.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. 5 l of the solution complies with identification A prescribed in the monograph on Calcium
gluconate (172).
C. Examine the chromatograms obtained in the test for radiochemical purity. The distribution of
the radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the solution is 6.0 to 8.5.
Radiochemical purity Examine by thin-layer chromatography (2.2.27) as described in the monograph on Radiopharmaceutical preparations (0125), using silica gel as the coating substance on a glassfibre sheet. Heat the plate at 110C for 10 min. Use a plate such that during development the
mobile phase migrates over a distance of 10 cm to 15 cm in about 10 min.
a) Apply to the plate 5 l to 10 l of the solution to be examined. Develop immediately over a path
of 10 cm to 15 cm using a 9 g/l solution of sodium chloride R. Allow the plate to dry. Determine the
distribution of radioactivity using a suitable detector. Impurities in colloidal form remain at the
starting point. Technetium gluconate complex and pertechnetate ion migrate near to the solvent

70-85
front.
b) Apply to the plate 5 l to 10 l of the solution to be examined and allow to dry. Develop over a
path of 10 cm to 15 cm using methyl ethyl ketone R. Dry in a current of warm air. Determine the
distribution of radioactivity using a suitable detector. Pertechnetate ion impurity migrates near to
the solvent front. Technetium gluconate complex and technetium in colloidal form remain at the
starting point.
The sum of the percentages of radioactivity corresponding to impurities in the chromatograms
obtained in test (a) and (b) does not exceed 10 per cent.
Physiological distribution Inject a volume not greater than 0.2 ml into the caudal vein of each of
three rats weighing 150 g to 250 g. Measure the radioactivity of the syringe before and after
injection. Sacrifice the rats 30 min after the injection. Remove at least 1 g of blood by a suitable
method and remove the kidneys, the liver, the bladder plus voided urine and the tail. Weigh the
sample of blood.
Determine the radioactivity in the organs, the blood sample and the tail using a suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125). Calculate
the percentage of radioactivity in each organ and in 1 g of blood with respect to the total radio-

70-86
activity calculated as the difference between the two measurements made on the syringe minus the
activity in the tail. Correct the blood concentration by multiplying by a factor of m/200 where m is
the body mass of the rat in grams.
In not fewer than two of the three rats used, the radioactivity in the kidneys is not less than
15 per cent, that in the bladder plus voided urine is not less than 20 per cent and that in the liver is
not more than 5 per cent. The radioactivity in the blood, after correction, is not more than
0.50 per cent.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Macrosalb Injection


Technetium[99mTc] Macrosalb Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0296]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) macrosalb injection is a sterile, apyrogenic suspension of human albumin in
the form of irregular insoluble aggregates obtained by denaturing human albumin in aqueous
solution; the particles are labelled with technetium-99m. The injection contains reducing
substances, such as tin salts in an amount not exceeding 3 mg of Sn per millilitre; it may contain a
suitable buffer such as acetate, citrate or phosphate buffer and also non-denatured human albumin
and an antimicrobial preservative such as benzyl alcohol. The human albumin employed complies
with the requirements prescribed in the monograph on Human albumin solution (0255). The injection
contains not less than 90.0 per cent and not more than 110.0 per cent of the declared technetium99m radioactivity at the date and hour stated on the label. Not less than 90 per cent of the
technetium-99m is bound to the particles of the suspension as determined by the test for nonfilterable radioactivity. The particles have a typical diameter between 10 m and 100 m. The
specific radioactivity is not less than 37 MBq of technetium-99m per milligram of aggregated
albumin at the date and hour of administration.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable
sterile and apyrogenic ingredients and calculating the ratio of radionuclidic impurities with
reference to the date and hour of administration.
CHARACTERS
A white suspension which may separate on standing.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. The tests for non-filterable radioactivity and particle size contribute to the identification of the
preparation.
C. Transfer 1 ml of the injection to a centrifuge tube and centrifuge at 2500 g for 5 min to 10 min.
Decant the supernatant liquid. To the residue add 5 ml of cupri-tartaric solution R2, mix and allow to
stand for 10 min. If necessary, heat to dissolve the particles and allow to cool. Add rapidly 0.5 ml

70-87
of dilute phosphomolybdotungstic reagent R, mixing immediately. A blue colour develops.
TESTS
pH (2.2.3). The pH of the injection is 3.8 to 7.5.
Non-filterable radioactivity Use a polycarbonate membrane filter 13 mm to 25 mm in diameter,
10 m thick and with circular pores 3 m in diameter. Fit the membrane into a suitable holder.
Place 0.2 ml of the injection on the membrane and filter, adding 20 ml of a 9 g/l solution of sodium
chloride R during the filtration. The radioactivity remaining on the membrane represents not less
than 90 per cent of the total radioactivity of the injection.
Particle size Examine using a microscope. Dilute the injection if necessary so that the number of
particles is just low enough for individual particles to be distinguished. Using a syringe fitted with a
needle having a calibre not less than 0.35 mm, place a suitable volume in a suitable counting
chamber such as a haemocytometer cell, taking care not to overfill the chamber. Allow the
suspension to settle for 1 min and carefully add a cover slide without squeezing the sample. Scan an
area corresponding to at least 5000 particles. Not more than 10 particles have a maximum
dimension greater than 100 m. No particle having a maximum dimension greater than 150 m is
present.
Aggregated albumin
Test solution. Transfer a volume of the injection expected to contain about 1 mg of aggregated
albumin to a centrifuge tube and centrifuge at about 2500 g for 5 min to 10 min. Decant the supernatant liquid. Resuspend the sediment in 2.0 ml of a 9 g/l solution of sodium chloride R. Centrifuge at
2500 g for 5 min to 10 min. Decant the supernatant liquid. Resuspend the sediment in 5.0 ml of
sodium carbonate solution R1. Heat in a water-bath at 80C to 90C to dissolve the aggregated
albumin. Allow to cool, transfer to a volumetric flask and dilute to 10.0 ml with sodium carbonate
solution R1.
Reference solutions. Prepare a range of reference solutions containing 0.05 mg to 0.2 mg of human
albumin per millilitre in sodium carbonate solution R1.
Introduce 3.0 ml of each solution separately into 25 ml flasks. To each flask add 15.0 ml of cupritartaric solution R2, mix and allow to stand for 10 min. Add rapidly 1.5 ml of dilute phosphomolybdotungstic reagent R and mix immediately. Allow to stand for 30 min and measure the absorbance
(2.2.25) at 750 nm using sodium carbonate solution R1 as the compensation liquid. Using the absorbances obtained with the reference solutions, draw a calibration curve and calculate the content of
aggregated albumin in the injection.
Tin
Test solution. To 1.0 ml of the injection add 1.0 ml of 2M hydrochloric acid. Heat in a water-bath for
30 min. Cool and centrifuge for 10 min at 300 g. Dilute 1.0 ml of the supernatant liquid to 25.0 ml
with 1M hydrochloric acid.
Reference solution. Dissolve 0.115 g of stannous chloride R in 1M hydrochloric acid and dilute to
1000.0 ml with the same acid.
To 1.0 ml of each solution add 0.4 ml of a 20 g/l solution of sodium lauryl sulphate R, 0.05 ml of
thioglycollic acid R, 0.1 ml of dithiol reagent R and 3.0 ml of 0.2M hydrochloric acid. Mix. Measure the
absorbance (2.2.25) of each solution at 540 nm, using 0.2M hydrochloric acid as the compensation
liquid. The absorbance of the test solution is not greater than that of the reference solution (3 mg
of Sn per millilitre).
Physiological distribution Inject a volume not greater than 0.2 ml into the caudal vein of each of
three rats weighing 150 g to 250 g. Kill the rats 15 min after the injection, remove the liver, the
spleen and the lungs and measure the radioactivity in the organs using a suitable instrument as
described in the monograph on Radiopharmaceutical preparations (0125). Measure the radioactivity in
the rest of the body, including the blood, after having removed the tail. Determine the percentage
of radioactivity in the lungs, the liver and the spleen from the expression:
A
100
B
A = radioactivity of the organ concerned,
B = total radioactivity in the liver, the spleen, the lungs and the rest of the body.
In not fewer than two of the three rats used, at least 80 per cent of the radioactivity is found in the
lungs and not more than a total of 5 per cent in the liver and spleen. The injection may be released
for use before completion of the test.

70-88
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Pyrogens It complies with the test for pyrogens prescribed in the monograph on Radiopharmaceutical preparations (0125). Inject into the animals not less than 0.1 ml per kilogram of the
rabbits mass. The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
The label states:
that the preparation should be shaken before use,
the quantity of tin per millilitre, if any,
that the preparation is not to be used if after shaking, the suspension does not appear
homogeneous.
__________________________________________________________________________________________________________ Ph Eur

TechnetiuM[99mTc] Medronate Injection


Technetium[99mTc] Medronate Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0641]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) medronate injection is a sterile solution which may be prepared by mixing
solutions of sodium methylenediphosphonate and a stannous salt with sodium pertechnetate
(99mTc) injection (fission or non-fission). The injection contains a variable quantity of tin (Sn) not
exceeding 3 mg/ml; it may contain antimicrobial preservatives, anti-oxidants, stabilisers and buffers.
The injection contains not less than 90.0 per cent and not more than 110.0 per cent of the
declared technetium-99m radioactivity at the date and hour stated on the label. Radioactivity
present as chemical forms other than technetium-99m medronate complex is not greater than
5.0 per cent of the total radioactivity.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable
sterile ingredients and calculating the ratio of radionuclidic impurities with reference to the date
and hour of administration.
CHARACTERS
A clear, colourless solution.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most
prominent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The distribution of
the radioactivity contributes to the identification of the preparation.
C. Examine by thin-layer chromatography (2.2.27), as described in the monograph on Radiopharmaceutical preparations (0125), using cellulose as the coating substance.
Test solution. Dilute the injection to be examined with water R to obtain a solution containing about
0.1 mg to 0.5 mg of sodium medronate per millilitre.
Reference solution. Dissolve a suitable quantity (1 mg to 5 mg) of medronic acid CRS in a mixture of a
9.0 g/l solution of sodium chloride R and water R and dilute to 10 ml with the same solvent so as to

70-89
obtain a solution similar to the test solution with regard to medronate and sodium chloride concentrations.
Apply separately to the plate 10 l of each solution. Develop over a path of 12 cm to 14 cm
(development time about 4 h) using a mixture of 20 volumes of 2-propanol R, 30 volumes of 1M
hydrochloric acid and 60 volumes of methyl ethyl ketone R. Allow the plate to dry in air and spray with
ammonium molybdate solution R4. Expose the plate to ultraviolet light at 254 nm for about 10 min.
The principal spot in the chromatogram obtained with the test solution is similar in position and
colour to the spot in the chromatogram obtained with the reference solution.
TESTS
pH (2.2.3). The pH of the solution is 3.5 to 7.5.
Radiochemical purity Examine by thin-layer chromatography (2.2.27), as described in the
monograph on Radiopharmaceutical preparations (0125), using silica gel as the coating substance on a
glass-fibre sheet. Use plates such that during development, the mobile phase migrates 10 cm to
15 cm in about 10 min. Determine hydrolysed technetium and technetium in colloidal form by test
(a) and pertechnetate ion by test (b).
(a) Apply to the plate 5 l to 10 l of the injection. Develop immediately over a path of 10 cm to
15 cm using a 136 g/l solution of sodium acetate R. Allow the plate to dry in air. Determine the
distribution of radioactivity using a suitable detector. Hydrolysed technetium and technetium in
colloidal form remain at the starting point. Technetium medronate complex and pertechnetate ion
migrate near to the solvent front.
(b) Apply to the plate 5 l to 10 l of the injection and dry quickly. Develop over a path of 10 cm.
to 15 cm using methyl ethyl ketone R. Allow the plate to dry. Determine the distribution of radioactivity using a suitable detector. Pertechnetate ion migrates near to the solvent front. Technetium
medronate complex and technetium in colloidal form remain at the starting-point.
The percentage of radioactivity corresponding to pertechnetate ion in the chromatogram
obtained in test (b) is not greater than 2.0 per cent and the sum of the percentages of radioactivity
corresponding to impurities in the chromatograms obtained in test (a) and test (b)
(including pertechnetate ion) is not greater than 5.0 per cent.
Tin
Test solution. Dilute 1.0 ml of the solution to 50.0 ml with 1M hydrochloric acid.
Reference solution. Dissolve 0.115 g of stannous chloride R in 1M hydrochloric acid and dilute to
1000.0 ml with the same acid.
To 1.0 ml of each solution add 0.4 ml of a 20 g/l solution of sodium lauryl sulphate R, 0.05 ml of
thioglycollic acid R, 0.1 ml of dithiol reagent R and 3.0 ml. of 0.2M hydrochloric acid. Mix. Measure the
absorbance (2.2.25) of each solution at 540 nm, using 0.2M hydrochloric acid as compensation liquid.
The absorbance of the test solution is not greater than that of the reference solution (3 mg of
Sn per millilitre).
Physiological distribution Inject a volume not greater than 0.2 ml, equivalent to not more than
0.05 mg of sodium medronate into a suitable vein such as a caudal vein or the saphenous vein of
each of three rats, each weighing 150 g to 250 g. Measure the radioactivity in the syringe before
and after injection. Kill the rats 2 h after the injection. Remove one femur, the liver, and some
blood. Weigh the blood. Remove the tail if a caudal vein has been used for the injection. Using a
suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125)
measure the radioactivity in the femur, liver, and blood, and in the tail if a caudal vein has been
used for the injection. Determine the percentage of radioactivity in each sample from the
expression:

70-90
A
100
B
A = radioactivity of the sample concerned,
B = total radioactivity, which is equal to the difference between the two measurements on
the syringe minus the radioactivity in the tail if a caudal vein has been used for the
injection.
Calculate the radioactivity per unit mass in the blood. Correct the blood concentration by
multiplying by a factor m/200 where m is the body mass of the rat in grams.
In not fewer than two of the three rats: not less than 1.5 per cent of the radioactivity is found in
the femur; not more than 1.0 per cent is found in the liver and not more than 0.05 per cent per
gram is found in the blood.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Mertiatide Injection


_

O
O

99m

Tc

2Na+
S

O
_

COO

Technetium[99mTc] Mertiatide Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [1372]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) mertiatide injection is a sterile solution which may be prepared by either
heating a mixture containing S-benzoylmercaptoacetyltriglycine (betiatide), a weak chelating agent
such as tartrate, a stannous salt and sodium pertechnetate (99mTc) injection (fission or non-fission),
or by mixing solutions of mercaptoacetyltriglycine (mertiatide), a stannous salt and
sodium pertechnetate (99mTc) injection (fission or non-fission) at alkaline pH. It may contain
stabilisers and a buffer. The injection contains not less than 90.0 per cent and not more than
110.0 per cent of the declared technetium-99m radioactivity at the date and time stated on the
label. Not less than 94 per cent of the radioactivity corresponds to technetium-99m in the form of
[99mTc]technetium mertiatide.
CHARACTERS
A clear, colourless solution.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph

70-91
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution.
Standardised technetium-99m solutions are available from laboratories recognised by the
competent authority. The most prominent gamma photon of technetium-99m has an energy of
0.140 MeV.
B. Examine the chromatogram obtained in test (b) for radiochemical purity. The principal peak in
the chromatogram obtained with the test solution has approximately the same retention time as the
principal peak in the chromatogram obtained with the reference solution.
TESTS
pH (2.2.3). The pH of the injection is 5.0 to 7.5.
Radiochemical purity
(a) Examine by ascending paper chromatography (2.2.26) as described in the monograph on Radiopharmaceutical preparations (0125), using a suitable paper as the stationary phase.
Test solution. The solution to be examined.
Apply 2 l of the test solution to the paper. Develop over a path of 15 cm using a mixture of 40
volumes of water R and 60 volumes of acetonitrile R. Allow the paper to dry and determine the
distribution of the radioactivity using a suitable detector. Not more than 2.0 per cent of the total
radioactivity is retained at the origin (Rf value 0.00.1).
(b) Examine by liquid chromatography (2.2.29).
Test solution. The solution to be examined.
Reference solution. Dissolve with heating on a water-bath 5 mg of S-benzyl mercaptoacetyltriglycine CRS
in 5 ml of water R. To 1 ml of this solution in a closed vial filled with nitrogen R, add 0.5 ml of a 40 g/l
solution of sodium potassium tartrate R, 25 l of a 4 g/l solution of stannous chloride R in 0.05M hydrochloric acid R and 370 MBq to 740 MBq of sodium pertechnetate (99mTc) injection (fission or nonfission) in a volume not exceeding 3 ml. Heat the mixture on a water-bath for 10 min and allow to
cool to room temperature.
The chromatographic procedure may be carried out using:
a stainless steel column 0.25 m long and 4.0 mm in internal diameter packed with octadecylsilyl
silica gel for chromatography R (5 m),
as mobile phase at a flow rate of 1.0 ml/min:
Mobile phase A. A mixture of 7 volumes of ethanol R with 93 volumes of a solution of a 1.36 g/l
solution of potassium dihydrogen phosphate R, adjusted to pH 6.0 with 0.1M sodium hydroxide,

70-92
Mobile phase B. A mixture of 10 volumes of water R with 90 volumes of methanol R,
a suitable radioactivity detector,
a 20 l loop injector.
Equilibrate the column with mobile phase A for 20 min. Inject the test solution and the reference
solution. Switch 10 min after each injection to mobile phase B and continue the chromatographic
procedure for 15 min.
The test is not valid unless in the chromatogram obtained with the test solution the principal peak
has approximately the same retention time as the principal peak in the chromatogram obtained with
the reference solution. In the chromatogram obtained with the test solution the sum of the areas
preceding the principal peak (corresponding to hydrophilic impurities, including [99mTc]pertechnetate) is not greater than 3.0 per cent of the sum of the areas of all peaks. The sum of the peaks
following the principal peak (corresponding to lipophilic impurities) is not greater than 4.0 percent
of the sum of the area of all peaks.
Not less than 94 per cent of the radioactivity corresponds to [99mTc]technetium mertiatide.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as prescribed in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Microspheres Injection


Technetium[99mTc] Microspheres Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0570]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) microspheres injection is a sterile, apyrogenic suspension of human albumin
which has been denatured to form spherical insoluble particles; the particles are labelled with
technetium-99m. The injection contains reducing substances, such as tin salts in an amount not
exceeding 3 mg of Sn per millilitre; it may contain a suitable buffer such as acetate, citrate or phosphate and additives such as wetting agents. The human albumin used complies with the requirements of the monograph on Human albumin solution (0255). The injection contains not less than
90.0 per cent and not more than 110.0 per cent of the declared technetium-99m radioactivity at
the date and hour stated on the label. Not less than 95 per cent of the technetium-99m is bound to
the particles of the suspension as determined by the test for non-filterable radioactivity. The
particles have a typical diameter between 10 m and 50 m. The radioactivity is not less than 185
MBq of technetium-99m per million particles at the date and hour of administration.
Technetium (99mTc) microspheres injection is prepared from sodium pertechnetate (99mTc)
injection (fission or non-fission) using suitable sterile and apyrogenic ingredients and calculating
the ratio of radionuclidic impurities with reference to the date and hour of administration.
CHARACTERS
A suspension of white, yellow or artificially coloured particles which may separate on standing.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.

70-93
B. The tests for non-filterable radioactivity and particle size contribute to the identification of the
preparation.
C. Transfer 1 ml of the injection to a centrifuge tube and centrifuge at 2500 g for 5 min to 10 min.
Decant the supernatant liquid. To the residue add 5 ml of cupri-tartaric solution R2, mix and allow to
stand for 10 min. If necessary, heat to dissolve the particles and allow to cool. Add rapidly 0.5 ml
of dilute phosphomolybdotungstic reagent R, mix immediately and allow to stand. A blue colour
develops.
TESTS
pH (2.2.3). The pH of the injection is 4.0 to 9.0.
Non-filterable radioactivity Use a polycarbonate membrane filter 13 mm to 25 mm in diameter,
10 m thick and with circular pores 3 m in diameter. Fit the membrane into a suitable holder.
Place 0.2 ml of the injection on the membrane and filter, adding 20 ml of a 9 g/l solution of sodium
chloride R during the filtration. The radioactivity remaining on the membrane represents not less
than 95 per cent of the total radioactivity of the injection.
Particle size Examine using a microscope. Dilute the injection if necessary so that the number of
particles is just low enough for individual particles to be distinguished. Using a syringe fitted with a
needle having a calibre not less than 0.35 mm, place a suitable volume in a suitable counting
chamber such as a haemocytometer cell, taking care not to overfill the chamber. Allow the
suspension to settle for 1 min and carefully add a cover slide without squeezing the sample. Scan an
area corresponding to at least 5000 particles. The particles have a uniform spherical appearance.
Not more than 10 particles have a maximum dimension greater than 75 m. No particle having a
maximum dimension greater than 100 m is present.
Number of particles Examine using a microscope. Fill a suitable counting chamber such as a
haemocytometer cell with a suitable dilution of the injection taking care that particles do not
separate during the transfer. Count the number of particles in the chamber. Repeat this procedure
twice and calculate the number of particles per millilitre of the injection.
Tin
Test solution. To 1.0 ml of the injection add 0.5 ml of sulphuric acid R and 1.5 ml of nitric acid R. Heat
and evaporate to approximately 1 ml. Add 2 ml of water R and evaporate again to approximately
1 ml. Repeat this procedure twice, cool and dilute to 25.0 ml with 1M hydrochloric acid.
Reference solution. Dissolve 0.115 g of stannous chloride R in 1M hydrochloric acid and dilute to
1000.0 ml with the same acid.
To 1.0 ml of each solution add 0.4 ml of a 20 g/l solution of sodium lauryl sulphate R, 0.05 ml of
thioglycollic acid R, 0.1 ml of dithiol reagent R and 3.0 ml of 0.2M hydrochloric acid. Mix. Measure the
absorbance (2.2.25) of each solution at 540 nm, using 0.2M hydrochloric acid as the compensation
liquid. The absorbance of the test solution is not greater than that of the reference solution (3 mg
of Sn per millilitre).
Physiological distribution Inject a volume not greater than 0.2 ml into a caudal vein of each of
three rats weighing 150 g to 250 g. Sacrifice the rats 15 min after the injection, remove the liver,
the spleen and the lungs and measure the radioactivity in the organs using a suitable instrument as
described in the monograph on Radiopharmaceutical preparations (0125). Measure the radioactivity in

70-94
the rest of the body, including the blood and voided urine, after having discarded the tail. Determine the percentage of radioactivity in the liver, the spleen and the lungs from the expression:
A
100
B
A = radioactivity of the organ concerned,
B = total radioactivity in the liver, the spleen, the lungs and the rest of the body, including
voided urine.
In not fewer than two of the three rats used, not less than 80 per cent of the radioactivity is found
in the lungs and not more than a total of 5 per cent in the liver and spleen. The injection may be
released for use before completion of the test.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Pyrogens It complies with the test for pyrogens prescribed in the monograph on Radiopharmaceutical preparations (0125). Inject not less than 0.1 ml per kilogram of the rabbits mass. The
injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
The label states:
the quantity of tin per millilitre, if any,
that the preparation should be shaken before use.
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Pentetate Injection


Technetium[99mTc] Pentetate Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0642]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) pentetate injection is a sterile solution which may be prepared by mixing
solutions of sodium diethylenetriaminepenta-acetate or calcium trisodium diethylenetriaminepentaacetate and a stannous salt with a solution of sodium pertechnetate (99mTc). It contains a variable
quantity of tin (Sn) not exceeding 1 mg per millilitre; it may contain suitable antimicrobial
preservatives, antioxidants, stabilisers and buffers. The injection contains not less than 90.0 per
cent and not more than 110.0 per cent of the declared technetium-99m radioactivity at the date
and hour stated on the label. Not less than 95.0 per cent of the radioactivity corresponds to
technetium-99m complexed with sodium pentetate or calcium trisodium pentetate.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable,
sterile ingredients and calculating the ratio of radionuclidic impurities with reference to the date
and hour of administration.
CHARACTERS
A clear, colourless or slightly yellow solution.
Technetium-99m has a half life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99

70-95
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. Examine the chromatograms obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the preparation.
C. Place in a clean, dry 10 ml glass tube a volume of the injection to be examined containing 2 mg
of pentetate. Dilute, if necessary, to 1 ml with water R. Place in a second tube 1 ml of water R
(blank). To each tube add 0.1 ml of a 1 g/l solution of nickel sulphate R, 0.5 ml of a 50 per cent V/V
solution of glacial acetic acid R and 0.75 ml of a 50 g/l solution of sodium hydroxide R. Mix and verify
that the pH is not above 5. To each tube add 0.1 ml of a 10 g/l alcoholic solution of dimethylglyoxime R. Mix and allow to stand for 2 min. Adjust the pH in each tube to not less than 12 by adding
a 100 g/l solution of sodium hydroxide R. Mix and check that the pH is not below 12. Allow to stand
for 2 min. Heat the tubes gently on a water-bath for 2 min. The solution in the tube containing the
injection to be examined remains clear and colourless throughout. The solution in the blank tube
becomes red on addition of dimethylglyoxime solution and a red precipitate is formed when the
tube is heated on a water-bath.
TESTS
pH (2.2.3). The pH of the injection is 4.0 to 7.5.
Radiochemical purity Examine by thin-layer chromatography (2.2.27) as described in the monograph on Radiopharmaceutical preparations (0125), using silica gel as the coating substance on a glassfibre sheet. Heat the plate at 110C for 10 min. Use a plate such that during development the
mobile phase migrates over a distance of 10 cm to 15 cm in about 10 min.
(a) Apply to the plate 5 l to 10 l of the injection to be examined. Develop immediately over a path
of 10 cm to 15 cm using a 9 g/l solution of sodium chloride R. Allow the plate to dry in air. Determine

70-96
the distribution of radioactivity using a suitable detector. Impurities in colloidal form remain at the
starting point. Technetium pentetate complex and pertechnetate ion migrate near to the solvent
front.
(b) Apply to the plate 5 l to 10 l of the injection to be examined and allow to dry. Develop over a
path of 10 cm to 15 cm using methyl ethyl ketone R. Allow the plate to dry. Determine the
distribution of radioactivity using a suitable detector. Pertechnetate ion migrates near to the solvent
front. Technetium pentetate complex and impurities in colloidal form remain at the starting point.
The sum of the percentages of radioactivity corresponding to impurities in the chromatograms
obtained in test (a) and (b) does not exceed 5.0 per cent.
Tin
Test solution. Dilute 1.5 ml of the injection to 25.0 ml with 1M hydrochloric acid.
Reference solution. Dissolve 0.115 g of stannous chloride R in 1M hydrochloric acid and dilute to
1000.0 ml with the same acid.
To 1.0 ml of each solution add 0.4 ml of a 20 g/l solution of sodium lauryl sulphate R, 0.05 ml of
thioglycollic acid R, 0.1 ml of dithiol reagent R and 3.0 ml of 0.2M hydrochloric acid. Mix. Measure the
absorbance (2.2.25) of each solution at 540 nm, using 0.2M hydrochloric acid as the compensation
liquid. The absorbance of the test solution is not greater than that of the reference solution (1 mg
of Sn per millilitre).
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Succimer Injection


Technetium[99mTc] Succimer Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0643]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) succimer injection is a sterile solution of meso-2,3-dimercaptosuccinic acid
labelled with technetium-99m. It contains a reducing substance, such as a tin salt in an amount not
exceeding 1 mg of Sn per millilitre, and may contain stabilisers, antioxidants such as ascorbic acid,
and inert additives. The injection contains not less than 90.0 per cent and not more than 110.0 per
cent of the declared technetium-99m radioactivity at the date and hour stated on the label. Not less
than 95.0 per cent of the radioactivity corresponds to technetium-99m succimer complex.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable
sterile ingredients and calculating the ratio of radionuclidic impurities with reference to the date
and hour of administration. Syringes for handling the eluate intended for labelling of the final
product, or for handling the final product should not contain rubber parts.
CHARACTERS
A clear, colourless solution.
Technetium-99m has a half life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prom-

70-97
inent gamma photon of technetium-99m has an energy of 0.140 MeV.
B. Examine the chromatogram obtained in the test for radiochemical purity. The distribution of the
radioactivity contributes to the identification of the preparation.
C. Place 1 ml of the injection to be examined in a test-tube and add 1 ml of a 20 g/l solution of
sodium nitroprusside R and 0.1 ml of glacial acetic acid R. Mix. Place carefully at the top of the solution
a layer of concentrated ammonia R. A violet ring develops between the layers.
TESTS
pH (2.2.3). The pH of the injection is 2.3 to 3.5.
Radiochemical purity Examine by thin-layer chromatography (2.2.27) as described in the monograph on Radiopharmaceutical preparations (0125), using silica gel as the coating substance on a glassfibre sheet. Heat the plate at 110C for 10 min. Use a plate such that during development the
mobile phase migrates over a distance of 10 cm to 15 cm in about 10 min.
Apply to the plate 5 l to 10 l of the injection to be examined. Develop immediately over a path
of 10 cm to 15 cm using methyl ethyl ketone R. Allow the plate to dry. Determine the distribution of
radioactivity using a suitable detector. Technetium succimer complex remains at the starting point.
Pertechnetate ion migrates near to the solvent front. Not less than 95.0 per cent of the total radioactivity is found in the spot corresponding to technetium succimer complex. The radioactivity
corresponding to pertechnetate ion represents not more than 2.0 per cent of the total radioactivity.
Tin
Test solution. Dilute 1.5 ml of the injection to be examined to 25.0 ml with 1M hydrochloric acid.
Reference solution. Dissolve 0.115 g of stannous chloride R in 1M hydrochloric acid and dilute to
1000.0 ml with the same acid.
To 1.0 ml of each solution add 0.4 ml of a 20 g/l solution of sodium lauryl sulphate R, 0.05 ml of

70-98
thioglycollic acid R, 0.1 ml of dithiol reagent R and 3.0 ml of 0.2M hydrochloric acid. Mix. Allow to stand
for 60 min. Measure the absorbance (2.2.25) of each solution at 540 nm, using 0.2M hydrochloric
acid as the compensation liquid. The absorbance of the test solution is not greater than that of the
reference solution (1 mg of Sn per millilitre).
Physiological distribution Inject a volume not greater than 0.2 ml and containing not more than
0.1 mg of dimercaptosuccinic acid into a suitable vein, such as a caudal vein or a saphenous vein,
of each of three rats each weighing 150 g to 250 g. Measure the radioactivity in the syringe before
and after the injection. Kill the rats 1 h after the injection. Remove the kidneys, the liver, the
stomach, the lungs and, if a caudal vein has been used for the injection, the tail. Using a suitable
instrument as described in the monograph on Radiopharmaceutical preparations (0125), determine the
radioactivity in the organs and, if a caudal vein has been used for injection, in the tail. Determine
the percentage of radioactivity in each organ with respect to the total radioactivity calculated as the
difference between the two measurements made on the syringe minus the activity in the tail (if a
caudal vein has been used for the injection).
In not fewer than two of the three rats used, the radioactivity in the kidneys is not less than
40 per cent, that in the liver is not more than 10.0 per cent, that in the stomach is not more than
2.0 per cent and that in the lungs is not more than 5.0 per cent.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125). Store protected from light.
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Technetium[99mTc] Tin Pyrophosphate Injection


Technetium[99mTc] Tin Pyrophosphate Injection complies with the requirements of the 3rd edition of the
European Pharmacopoeia [0129]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Technetium (99mTc) tin pyrophosphate injection is a sterile, apyrogenic solution which may be
prepared by mixing solutions of sodium pyrophosphate and stannous chloride with
sodium pertechnetate (99mTc) injection (fission or non-fission). The injection contains not less than
90.0 per cent and not more than 110.0 per cent of the declared technetium-99m radioactivity at
the date and hour stated on the label. Not less than 90 per cent of the radioactivity corresponds to
technetium-99m complexed with tin pyrophosphate. The injection contains a quantity of sodium
pyrophosphate (Na4P2O7,10H2O) that may vary from 1 mg to 50 mg per millilitre and a variable
quantity of tin (Sn) not exceeding 3.0 mg per millilitre.
It is prepared from sodium pertechnetate (99mTc) injection (fission or non-fission) using suitable
sterile, apyrogenic ingredients and calculating the ratio of radionuclidic impurities with reference to
the date and hour of administration.
CHARACTERS
A clear, colourless solution.
Technetium-99m has a half-life of 6.02 h and emits gamma radiation.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as described in the monograph on
Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of a
standardised technetium-99m solution either by direct comparison or by using an instrument
calibrated with the aid of such a solution. Standardised technetium-99m and molybdenum-99
solutions are available from laboratories recognised by the competent authority. The most prominent gamma photon of technetium-99m has an energy of 0.140 MeV.

70-99
B. Examine the chromatograms obtained in the test for radiochemical purity. The distribution of
radioactivity contributes to the identification of the injection.
C. To 1 ml add 1 ml of acetic acid R. Heat on a water-bath for 1 h. After cooling, add 10 ml of nitrovanadomolybdic reagent R and allow to stand for 30 min. A yellow colour develops.
D. To 1 ml add 2 ml of a 30 per cent V/V solution of sulphuric acid R, 1 ml of hydrochloric acid R,
0.05 ml of thioglycollic acid R, 0.4 ml of a 20 g/l solution of sodium lauryl sulphate R and 0.1 ml of
dithiol reagent R and allow to stand for 30 min. A pink colour develops.
TESTS
pH (2.2.3). The pH of the injection is 6.0 to 7.0.
Radiochemical purity
(a) Examine by thin-layer chromatography (2.2.27), as described in the monograph on Radiopharmaceutical preparations (0125) using silica gel as the coating substance on a glass-fibre sheet.
Heat the plate at 110C for 10 min. The plate used should be such that during development the
mobile phase migrates over a distance of 10 cm to 15 cm in about 10 min.
Apply to the plate 5 l to 10 l of the injection and dry in a stream of nitrogen. Develop over a
path of 10 cm to 15 cm using methyl ethyl ketone R through which nitrogen has been bubbled in the
chromatography tank for 10 min immediately before the chromatography. Allow the plate to dry.
Determine the distribution of radioactivity using a suitable detector. The technetium-99m tin
pyrophosphate complex remains at the starting-point and pertechnetate ion migrates with an Rf of
0.95 to 1.0.
(b) Examine by thin-layer chromatography (2.2.27), as described in the monograph on Radiopharmaceutical preparations (0125) using silica gel as the coating substance on a glass-fibre sheet.
Heat the plate at 110C for 10 min. The plate used should be such that during development the
mobile phase migrates over a distance of 10 cm to 15 cm in about 10 min.
Apply to the plate 5 l to 10 l of the injection. Develop immediately over a path of 10 cm to
15 cm using a 136 g/l solution of sodium acetate R. Allow the plate to dry and measure the
distribution of radioactivity using a suitable detector. Impurities in colloidal form remain at the
starting-point and technetium-99m tin pyrophosphate complex and pertechnetate ion migrate with
an Rf of 0.9 to 1.0.
Add together the percentages of radioactivity corresponding to impurities in the chromatograms
obtained in test (a) and test (b). The sum does not exceed 10 per cent.
Sodium pyrophosphate
Test solution. Use 1 ml of the injection to be examined or a suitable dilution of it.
Reference solutions. Using a solution containing sodium pyrophosphate R and stannous chloride R in the
same proportions as in the injection to be examined, prepare a range of solutions and dilute to the
same final volume with water R.
To the test solution and to 1 ml of each of the reference solutions add successively 10 ml of a 1 g/l
solution of disodium hydrogen phosphate R, 10 ml of iron standard solution (8 ppm Fe) R, 5 ml of glacial
acetic acid R and 5 ml of a 1 g/l solution of hydroxylamine hydrochloride R. Dilute each solution to
40 ml with water R and heat in a water-bath at 40C for 1 h. To each solution add 4 ml of a 1 g/l
solution of phenanthroline hydrochloride R and dilute to 50.0 ml with water R. Measure the absorbance
(2.2.25) of each solution at 515 nm using as the compensation liquid a reagent blank containing
hydrochloric acid (1.1 g/l HCl) instead of the iron standard solution (8 ppm Fe) R. Using the
absorbances obtained with the reference solutions, draw a calibration curve and calculate the
concentration of sodium pyrophosphate in the injection to be examined.
Tin
Test solution. Use 1 ml of the injection to be examined or a suitable dilution of it.

70-100
Reference solutions. Using a solution in hydrochloric acid (6.2 g/l HCl) containing sodium
pyrophosphate R and stannous chloride R in the same proportions as in the injection to be examined,
prepare a range of solutions and dilute to the same volume with hydrochloric acid (6.2 g/l HCl).
To the test solution and to 1 ml of each of the reference solutions add 2 ml of a 300 g/l solution of
sulphuric acid R, 1 ml of hydrochloric acid R, 0.05 ml of thioglycollic acid R, 0.4 ml of a 20 g/l solution of
sodium lauryl sulphate R and 0.1 ml of dithiol reagent R and dilute to 15 ml with hydrochloric acid
(6.2 g/l HCl). Allow the solutions to stand for 30 min and measure the absorbance (2.2.25) of each
solution at 530 nm, using as the compensation liquid a reagent blank containing the same quantity
of sodium pyrophosphate R as the injection to be examined. Using the absorbances obtained with the
reference solutions, draw a calibration curve and calculate the concentration of tin in the injection
to be examined.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Pyrogens It complies with the test for pyrogens prescribed in the monograph on Radiopharmaceutical preparations (0125). Inject not less than 0.1 ml per kilogram of the rabbits mass. The
injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised technetium-99m solution or
by measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
The label states, in particular, the quantity of sodium pyrophosphate per millilitre and the
quantity of tin per millilitre.
__________________________________________________________________________________________________________ Ph Eur

Thallous[201Tl] Chloride Injection


Thallous[201Tl] Chloride Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0571]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Thallous (201Tl) chloride injection is a sterile solution of thallium-201 in the form of thallous
chloride. It may be made isotonic by the addition of sodium chloride and may contain a suitable
antimicrobial preservative such as benzyl alcohol. Thallium-201 is a radioactive isotope of thallium
formed by the decay of lead-201. Lead-201 is a radioactive isotope of lead and may be obtained by
irradiation, with protons of suitable energy, of thallium which may be enriched in thallium-203.
Thallium-201 may be separated from lead-201 by passing through a column of an ion-exchange
resin. The injection contains not less than 90.0 per cent and not more than 110.0 per cent of the
declared thallium-201 radioactivity at the date and hour stated on the label. Not more than 2.0 per
cent of the total radioactivity is due to thallium-202 and not less than 97.0 per cent is due to
thallium-201. Not less than 95.0 per cent of the radioactivity is due to thallium in the form of
thallous ions. The specific radioactivity is not less than 3.7 GBq per milligram of thallium.
CHARACTERS
A clear, colourless solution.
Thallium-201 has a half-life of 3.05 days and emits gamma radiation and X-rays.
IDENTIFICATION
A. Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised thallium-201 solution when measured either by direct comparison or by
use of an instrument calibrated with the aid of such a solution. Standardised thallium-201 and
thallium-202 solutions are available from laboratories recognised by the competent authority. The
most prominent gamma photons have energies of 0.135 MeV, 0.166 MeV and 0.167 MeV. The Xrays have energies of 0.069 MeV to 0.083 MeV.

70-101
B. Examine the electrophoretogram obtained in the test for radiochemical purity. The distribution
of radioactivity contributes to the identification of the preparation.
TESTS
pH (2.2.3). The pH of the injection is 4.0 to 7.0.
Radionuclidic purity Record the gamma-ray and X-ray spectrum as described in the monograph
on Radiopharmaceutical preparations (0125) using a suitable instrument calibrated with the aid of
standardised thallium-201 and thallium-202 solutions. The spectrum does not differ significantly
from that of the standardised thallium-201 solution. Determine the relative amounts of thallium201 and thallium-202 and other radionuclidic impurities present. Thallium-202 has a half-life of
12.2 days and its most prominent gamma photon has an energy of 0.440 MeV. Thallium-200 has a
half-life of 1.09 days and its most prominent gamma photons have energies of 0.368 MeV,
0.579 MeV, 0.828 MeV and 1.206 MeV. Lead-201 has a half-life of 9.4 h and its most prominent
gamma photon has an energy of 0.331 MeV. Lead-203 has a half-life of 2.17 days and its most
prominent gamma photon has an energy of 0.279 MeV. Not more than 2.0 per cent of the total

70-102
radioactivity is due to thallium-202 and not less than 97.0 per cent is due to thallium-201.
Radiochemical purity Examine by zone electrophoresis (2.2.31), using a strip of suitable cellulose
acetate, 150 mm by 25 mm, as the support and a 18.6 g/l solution of sodium edetate R as the
electrolyte solution. Soak the strip in the electrolyte solution for 45 min to 60 min. Remove the
strip with forceps taking care to handle the outer edges only. Place the strip between two absorbent
pads and blot to remove excess solution.
Test solution. Mix equal volumes of the injection to be examined and the electrolyte solution.
Apply not less than 5 l of the test solution to the centre of the strip and mark the point of
application. Apply an electric field of 17 V per centimetre for 30 min. Allow the strip to dry in air.
Determine the distribution of radioactivity using suitable equipment. Not less than 95.0 per cent of
the radioactivity migrates towards the cathode.
Thallium To 0.5 ml of the injection add 0.5 ml of hydrochloric acid (220 g/l HCl) and 0.05 ml of
bromine water R and mix. Add 0.1 ml of a 30 g/l solution of sulphosalicylic acid R. After decolorisation
add 1.0 ml of a 1 g/l solution of rhodamine B R. Add 4 ml of toluene R and shake for 60 s. Separate
the toluene layer. The toluene layer is not more intensely coloured than the toluene layer of a
standard prepared at the same time in the same manner using 0.5 ml of thallium standard solution
(10 ppm Tl) R.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable counting equipment by comparison with a standardised thallium-201 solution or by
measurement in an instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
__________________________________________________________________________________________________________ Ph Eur

Water[15O] Injection
1/01
Water[15O] Injection complies with the requirements of the 3rd edition of the European Pharmacopoeia
[1582]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Water (15O) injection is a sterile solution of [15O]water for diagnostic use. The injection contains
not less than 90.0 per cent and not more than 110.0 per cent of the declared oxygen-15 radioactivity at the date and time stated on the label. Not less than 99 per cent of the total radioactivity
corresponds to oxygen-15 in the form of water.
PRODUCTION
RADIONUCLIDE PRODUCTION
Oxygen-15 is a radioactive isotope of oxygen which may be produced by various nuclear reactions
such as proton irradiation of nitrogen-15 or deuteron irradiation of nitrogen-14.
RADIOCHEMICAL SYNTHESIS
In order to recover oxygen-15 as molecular oxygen from the nitrogen target gas, carrier oxygen is
added at concentrations generally ranging from 0.2 per cent V/V to 1.0 per cent V/V. [15O]Water
can be prepared from [15O]oxygen by reaction with hydrogen using a suitable catalyst.
An alternative method is to produce [15O]water in-target by adding hydrogen to the irradiated
target gas at a concentration generally ranging from 2 per cent V/V to 5 per cent V/V.
The [15O]water vapour contained in the gas-stream is either bubbled through a reservoir of a sterile
9 g/l solution of sodium chloride, or is exchanged by diffusion into such a solution through a
membrane filter for dialysis.
Ammonia is a possible chemical impurity in [15O]water. This may arise either from catalytic

70-103
conversion of hydrogen and nitrogen on the catalyst or by radiolysis if in-target production is
used. In addition, there is the possibility of contamination by oxygen-15-labelled oxides of
nitrogen. Although these contaminants can be effectively removed from the gas phase by soda lime
and charcoal adsorbers, they may break through and be present in the final preparation.
Production systems and their performance comply with the requirements prescribed in the monograph on Radiopharmaceutical preparations (0125).
STARTING MATERIALS
Target materials comply with the requirements prescribed in the monograph on Radiopharmaceutical
preparations (0125).
CHARACTERS
A clear, colourless solution.
Oxygen-15 has a half-life of 2.04 min and emits positrons with a maximum energy of 1.732 MeV,
followed by annihilation gamma radiation of 0.511 MeV.
IDENTIFICATION
A. Record the gamma-ray spectrum using a suitable instrument as prescribed in the monograph
on Radiopharmaceutical preparations (0125). The only gamma photons have an energy of 0.511 MeV
and, depending on the measurement geometry, a sum peak of 1.022 MeV may be observed.
B. It complies with the test for radionuclidic purity (see Tests).
C. Examine the chromatogram obtained in the test for radiochemical purity. The retention time of
the second peak is due to the radioactivity eluting in the void volume.
TESTS
pH (2.2.3). The pH of the injection is 5.5 to 8.5.
Chemical purity
(a) Ammonium (2.4.1).1 ml complies with the limit test for ammonium (10 ppm).
(b) Nitrates To 1 ml add 49 ml of nitrate-free water R. Place 5 ml of this solution in a test-tube
immersed in iced water, add 0.4 ml of a 100 g/l solution of potassium chloride R, 0.1 ml of
diphenylamine solution R and, dropwise with shaking, 5 ml of sulphuric acid R. Transfer the tube to a
water-bath at 50C. After 15 min, any blue colour in the solution is not more intense than that in a
standard prepared at the same time in the same manner using a mixture of 4.5 ml of nitrate-free
water R and 0.5 ml of nitrate standard solution (2 ppm NO3) R (10 ppm).
The injection may be released for use before completion of tests (a) and (b).
Radionuclidic purity
Record the gamma-ray spectrum using a suitable instrument as described in the monograph
on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from that of
a standardised fluorine-18 solution. Standardised fluorine-18 solutions are available from the
laboratories recognised by the competent authority.
The half-life as measured by methods described in the monograph on Radiopharmaceutical
preparations (0125) is between 1.9 min and 2.2 min. Not less than 99 per cent of total radioactivity
corresponds to oxygen-15.
The injection may be released for use before completion of the test.
Radiochemical purity Examine by liquid chromatography (2.2.29).
Test solution. The preparation to be examined.
The chromatographic procedure may be carried out using:
a column 0.25 m long and 4.0 mm in internal diameter packed with aminopropylsilyl silica gel for

70-104
chromatography R (10 m),
as mobile phase at a flow rate of 1 ml/min a 10 g/l solution of potassium dihydrogen phosphate R
adjusted to pH 3 with phosphoric acid R,
a suitable radioactivity detector,
a loop injector,
an internal recovery detection system, consisting of a loop of the chromatographic tubing
between the injector and the column through the radioactivity detector, which has been
calibrated for count recovery,
maintaining the column at a constant temperature between 20C and 30C.
Inject the test solution. Continue the chromatography for 10 min. In the chromatogram
obtained, the first peak corresponds to the injected radioactivity of the test solution, the second
peak corresponds to the amount of radioactivity as [15O]water. Calculate the percentage content of
[15O]water from the areas of the peaks in the chromatogram obtained with the test solution. Not
less than 99 per cent of the total radioactivity injected corresponds to oxygen-15 in the form of
water.
The injection may be released for use before completion of the test.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
Bacterial endotoxins (2.6.14). Not more than 175/V I.U. of endotoxin per millilitre, V being the
maximum administered volume in millilitres. The injection may be released for use before
completion of the test.
RADIOACTIVITY
Measure the radioactivity as described in the monograph on Radiopharmaceutical preparations (0125)
using suitable equipment by comparison with a standardised fluorine-18 solution or by using an
instrument calibrated with the aid of such a solution.
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
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Tritiated[3H] Water Injection


Tritiated[3H] Water Injection complies with the requirements of the 3rd edition of the European
Pharmacopoeia [0112]. These requirements are reproduced after the heading Definition below.
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DEFINITION
Tritiated (3H) water injection is water for injections in which some of the water molecules contain
tritium atoms in place of protium atoms. It may be made isotonic by the addition of sodium
chloride. Tritium (3H) may be obtained by the neutron irradiation of lithium. The injection
contains not less than 90.0 per cent and not more than 110.0 per cent of the declared tritium
activity at the date stated on the label.
CHARACTERS
A clear, colourless liquid.
Tritium has a half-life of 12.3 years and emits beta radiation.
IDENTIFICATION
Record the beta-ray spectrum by the method prescribed in the test for radionuclidic purity. The
spectrum does not differ significantly from that of a standardised tritiated (3H) water. Standardised
tritiated (3H) water is available from laboratories recognised by the competent authority. The
maximum energy of the beta radiation is 0.019 MeV.
TESTS
pH (2.2.3). The pH of the injection is 4.5 to 7.0.
Radionuclidic purity
(a) Mix 100 l of a suitable dilution of the injection with 10 ml of a scintillation liquid consisting of

70-105
1000 ml of dioxan R, 100 g of naphthalene R, 7 g of diphenyloxazole R and 0.3 g of
methylphenyloxazolylbenzene R, the reagents being of an analytical grade suitable for liquid scintillation. Measure the radioactivity of the mixture in a liquid scintillation counter fitted with a
discriminator. The count should be about 5000 impulses per second at the lowest setting of the
discriminator. Record the count at different discriminator settings. For each measurement count at
least 10,000 impulses over a period of at least 1 min. Immediately determine in the same conditions
the count for a standardised tritiated (3H) water having approximately the same activity.
Plot the counts at each discriminator setting, correcting for background activity, on semilogarithmic paper, the discriminator settings being in arbitrary units as the abscissae. The vertical
distance between the two curves obtained is constant. They obey the mathematical relationship:

70-106
A1 A2

B1 B 2
100 < 20
A1
B1
A1 = radioactivity recorded for the standardised preparation at the lowest discriminator
setting,
B1 = radioactivity recorded for the preparation to be examined at the lowest discriminator
setting,
A2 = radioactivity recorded for the standard at the discriminator setting such that A2 Al
103,
B2 = radioactivity recorded for the preparation to be examined at the latter discriminator
setting.
(b) Record the gamma-ray spectrum. The instrument registers only background activity.
Radiochemical purity Place a quantity of the injection equivalent to about 2 Ci (74 kBq),
diluted to 50 ml with water R, in an all-glass distillation apparatus of the type used for the
determination of Distillation range (2.2.11). Determine the radioactive concentration as described in
the monograph on Radiopharmaceutical preparations (0125). Distil until about 25 ml of distillate has
been collected. Precautions must be taken to avoid contamination of the air. If the test is carried
out in a fume cupboard, the equipment must be protected from draughts. Determine the radioactive concentration of the distillate and of the liquid remaining in the distillation flask. Neither of
the radioactive concentrations determined after distillation differs by more than 5 per cent from the
value determined before distillation.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125).
RADIOACTIVITY
Determine the radioactivity using a liquid scintillation counter as described in the monograph on
Radiopharmaceutical preparations (0125).
STORAGE
See Radiopharmaceutical preparations (0125).
LABELLING
See Radiopharmaceutical preparations (0125).
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Xenon[133Xe] Injection
Xenon[133Xe] Injection complies with the requirements of the 3rd edition of the European Pharmacopoeia
[0133]. These requirements are reproduced after the heading Definition below.
Ph Eur ___________________________________________________________________________________________________________

DEFINITION
Xenon (133Xe) injection is a sterile solution of xenon-133 that may be made isotonic by the addition
of sodium chloride. Xenon-133 is a radioactive isotope of xenon and is obtained by separation
from the other products of uranium fission. The injection contains not less than 80 per cent and
not more than 130 per cent of the declared xenon-133 radioactivity at the date and hour stated on
the label.
The injection is presented in a container that allows the contents to be removed without
introducing air bubbles. The container is filled as completely as possible and any gas bubble
present does not occupy more than 1 per cent of the volume of the injection as judged by visual
comparison with a suitable standard.
CHARACTERS
A clear, colourless solution.
Xenon-133 has a half-life of 5.29 days and emits beta and gamma radiation and X-rays.
IDENTIFICATION
Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly from

70-107
that of a standardised xenon-133 solution in a 9 g/l solution of sodium chloride R, apart from any
differences attributable to the presence of xenon-131m and xenon-133m. If standardised xenon133 solutions are not readily available, suitable standardised ionisation chambers are obtainable
from laboratories recognised by the relevant competent authority. The most prominent gamma
photon of xenon-133 has an energy of 0.081 MeV and there is an X-ray (resulting from internal
conversion) of 0.030 MeV to 0.035 MeV. Xenon-131m has a half-life of 11.9 days and emits a
gamma photon of 0.164 MeV. Xenon-133m has a half-life of 2.19 days and emits a gamma photon
of 0.233 MeV.
TESTS
pH (2.2.3). The pH of the injection is 5.0 to 8.0.
Radionuclidic purity
(a) Record the gamma-ray and X-ray spectrum using a suitable instrument as described in the
monograph on Radiopharmaceutical preparations (0125). The spectrum does not differ significantly
from that of a standardised xenon-133 solution in a 9 g/l solution of sodium chloride R, apart from
any differences attributable to the presence of xenon-131 m and xenon-133m.
(b) Transfer 2 ml of the injection to an open flask and pass a current of air through the solution for
30 min, taking suitable precautions concerning the dispersion of radioactivity. Measure the residual
beta and gamma activity of the solution. The activity does not differ significantly from the
background activity detected by the instrument.
Sterility It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical
preparations (0125). The injection may be released for use before completion of the test.
RADIOACTIVITY
Weigh the container with its contents. Determine its total radioactivity using suitable counting
equipment by comparison with a standardised xenon-133 solution or by measurement in an instrument calibrated with the aid of such a solution, operating in strictly identical conditions. If an
ionisation chamber is used its inner wall should be such that the radiation is not seriously
attenuated. Remove at least half the contents and re-weigh the container. Measure the radioactivity
of the container and the remaining contents as described above. From the measurements, calculate
the radioactive concentration of xenon-133 in the injection.
STORAGE
See the monograph on Radiopharmaceutical preparations (0125).
LABELLING
See the monograph on Radiopharmaceutical preparations (0125).
CAUTION
Significant amounts of xenon-133 may be present in the closures and on the walls of the container. This must be
taken into account in applying the rules concerning the transport and storage of radioactive substances and in
disposing of used containers.
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