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J ournal of Chemical Technology

Vol. 13, J uly 2006, pp. 353-359








Sensitive bromatometric methods for the assay of metaprolol tartrate
in dosage forms
K Basavaiah
1*
, B C Somashekar
1
& V Ramakrishna
2

1
Department of Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India
2
Department of Pharmaceutical Chemistry, Govt. College of Pharmacy, Bangalore 560 027, India
Email: basavaiahk@yahoo.co.in
Received 25 July 2005; revised received 12 April 2006; accepted 1 May 2006
One titrimetric and two spectrophotometric methods are described for the determination of metaprolol tartrate (MPT)
using bromate-bromide mixture and two dyes, methyl orange and indigo carmine, as reagents. In titrimetry, an acidified
solution of MPT is reacted with a known excess of bromate-bromide mixture and after a pre-determined time, the unreacted
bromine is determined by iodometric titration. The spectrophotometric methods involve the addition of a known excess of
bromate-bromide mixture to MPT in acidic medium followed by determination of the residual bromine by reacting with
fixed amount of either methyl orange and measuring the absorbance at 520 nm (Method A) or indigo carmine and measuring
the absorbance at 610 nm (Method B). In all the methods, amount of bromine reacted corresponds to the amount of MPT.
The working conditions of the methods have been optimised. Titrimetry allows the determination of MPT in 2.5 - 7.5 mg
range and the calculations are based on a 1:1(MPT : KBrO
3
) reaction stoichiometry. In the spectrophotometric methods,
Beers law is valid over the concentration ranges 0.5 -5.0 and 1.5 - 15.0 g mL
-1
MPT for method A and method B,
respectively. Method A with a molar absorptivity of 8.17 10
4
L mol
-1
cm
-1
is more sensitive than method B ( =2.70 10
4

L mol
-1
cm
-1
)

. The limits of detection and quantification are reported for both the methods. The methods could usefully be
applied to routine quality control of tablets containing MPT. No interference was observed from common pharmaceutical
adjuvants. Statistical comparison of the results with those obtained by an established UV-spectrophotometric method
showed excellent agreement and indicated no significant difference in accuracy and precision. The reliability of the methods
was further ascertained by recovery studies.
Keywords: Metaprolol tartrate, Assay, Bromate-bromide, Dyes, Dosage forms
IPC Code: A61K9/08

Beta blockers have been in clinical use for over 30
years and have an accepted role in the treatment of
high blood pressure, the secondary prevention of
myocardial infarction and in the treatment of
arrhythmias. Metaprolol tartrate (MPT), () -
(isopropylamino-3-[4-(2-methoxyethyl) phenoxy]-2-
propanol tartrate (Fig. 1), is known as a cardio
selective beta adrenergic receptor blocker
1
. Nearly
200 articles have appeared since the early 1980s
describing the detection and determination of this
drug using a variety of analytical techniques, but a
large number of them are devoted to the analysis of
biological samples. The drug is official in the United
States Pharamcopoeia
2
which describes a non-
aqueous titrimetric procedure for bulk drug and a high
performance liquid chromatographic method for assay
in tablets. For the determination of this drug in dosage
forms, several techniques including UV-
spectrophotometry
3-6
, near infrared spectroscopy
7
,
fluorimetry
8,9
, AAS
10,11
, liquid chromatography
12
,
high performance liquid chromatography
13-16
, high
performance thin layer chromatography
17
, gas
chromatography-mass spectroscopy
18
, densitometry
19
,
ion-selective electrode based potentiometry
20
, and
voltammetry
21
have been reported. But most of the
above techniques are tedious, time-consuming and
difficult to perform besides involving expensive
instrumental setup, and are applicable for assay in
combined dosage forms.

Fig 1 Structure of MPT
INDIAN J CHEM. TECHNOL., J ULY 2006


354
From a pharmaceutical analysis stand point, it is
highly desirable if the assay methods are simple, rapid
and affordable by small-scale industrial laboratories,
without a compromise on the requirements of
sensitivity, selectivity, and accuracy and precision. In
this respect, titrimetry and spectrophotometry
continue to be used in industrial quality control
laboratories because of their low cost, versatility of
applications and ease of operation. However, there is
only one report
22
on the titrimetric determination of
MPT and the method uses metavanadate as the
oxidimetric reagent which is performed in high H
2
SO
4

concentration.
MPT has rendered itself to analysis by visible
spectrophotometry through several chemical
reactions. Nitration of MPT to produce a yellow
derivative in H
2
SO
4
medium was introduced as a
quantitative method by Sanghavi and Vyas
23
.
Formation of a yellow colour on reacting the drug
with iron(III) chloride
24
in HCl medium has been the
basis of assay in pharmaceutical preparations. Ersoy
and Kocaman
25
have used bromothymol blue as ion-
pair reagent for the sensitive determination of MPT.
Based on a similar reaction but using benzyl orange as
a chromogenic reagent, a quantitative assay method
has been proposed by Vujic et al.
26
. A stable greenish
- yellow chromophore resulting from the reaction of
MPT with 1-fluoro-2,4-dinitro benzene (FDNB) in
tetraborate - HCl medium was used by Shingbal and
Bhangle
27
. In a method presented by one of the same
authors
28
, MPT was reacted with acetaldehyde and
chloranil in the presence of Ag
2
O to produce a blue
chromogen measurable at 680 nm. There are two
reports on the use of charge-transfer complex
reactions employing 4-chloro-7-nitro-2,1,3-
benzoxadiazole (NBD-Cl)
29
and tetracyano ethylene
(TCNE) or chloranilic acid(CAA)
10
as - acceptors
for the determination of MPT. A method
10
has been
proposed whereby the chelate formed with copper(II)
in the presence of CS
2
was extracted into isobutyl
methyl ketone before absorbance measurement. Other
method determining MPT involved the formation of
copper(II)dithiocarbamate complex
11
by derivatisation
the secondary amino group of the drug with CS
2
and
CuCl
2
before extracting into chloroform, and
measurement. But, most of the currently available
spectrophotometric methods suffer from one or the
deficiency such as poor sensitivity, narrow linear
range of response, stringent experimental conditions
like heating or extraction step, and/or use of
expensive chemicals (Table 1).
In the present study, two techniques, titrimetry and
spectrophotometry have been employed for the assay
of MPT using bromate-bromide mixture as the
Table 1Comparison of the existing spectrophotometric methods with the proposed methods for MPT
Sl No. Reagent/s used*
max,
nm Linear range, g ml
-1
Remarks Ref.
1 KNO
3
440 <120 Less sensitive 23
2 Iron (III) choride 380 40 - 200 Less sensitive 24
3 Bromothymol
blue
410 2 - 14 Requires rigid pH control, involves liquid-liquid
extraction
25
4 Benzyl orange 401 3.4 - 34.2 Requires rigid pH control, involves liquid-liquid
extraction
26
5 FDNB 380
-------
Involves heating a 75 C for 40 min and uses an
expensive chemical
27
6 Actaldehyde-
chloranil- Ag
2
O
680 25 - 75 Requires heating at 75 C for 10 min, narrow
linear range of response and less sensitive
28
7 NBD - Cl 470 0.4 - 60.0 Requires partially non-aqueous medium and
expensive chemical
29
8 a) TCNE
b) CAA
415
510
10 -170
(3.49 10
3
)
20 -230
(1.73 10
3
)
Requires non-aqueous medium; less sensitive 10
9 CS
2
-CuCl
2
435.4 Upto 60 (1.08 10
4
) Involves liquid-liquid extraction; less sensitive 10
10 CS
2
-CuCl
2
-
dithiocarbamate
440 11 - 55 Involves liquid-liquid extraction and less
sensitive
11
11 a) KBrO
3
-KBr/
methyl orange
b) KBrO
3
-KBr/
indigo carmine
520
610
0.5 - 5.0
(8.17 10
4
)
1.5 - 15.0
(2.7 10
4
)
No heating or extraction step, long linear range of
response, highly sensitive and use inexpensive
chemicals
Present
methods
Figures in the parentheses are molar absorptivities in l mol
-1
cm
-1

BASAVAIAH et al.: SENSITIVE BROMATOMETRIC METHODS FOR THE ASSAY OF METAPROLOL TARTRATE


355
oxidimetric reagent and methyl orange and indigo
carmine as the spectrophotometric reagents. The
methods, when applied to the assay of MPT in dosage
forms, have been found to be convenient and are free
from difficulties encountered in many of the existing
methods.

Experimental Procedure
Reagents and materials
A Systronics Model 106 digital spectrophotometer
provided with matched 1-cm quartz cells was used for
all absorbance measurements. All chemicals used
were of analytical reagent grade and distilled water
was used to prepare all solutions. Bromate-bromide
mixture (510
-3
M KBrO
3
- 5010
-3
M KBr) was
prepared by dissolving accurately weighed 0.8 g of
KBrO
3
(Sarabhai M Chemicals, Baroda, India) and
6 g of KBr (Indian Drugs and Pharmaceuticals Ltd,
Hyderabad, India) in water and diluting to 1 litre in a
calibrated flask, and the reagent was used in
titrimetric work. A 0.03 M sodium thiosulphate
solution was prepared by dissolving about 7.45 g of
compound (Sisco Chem Industries, Mumbai, India) in
1 litre of water and standardized
30
. A 10% potassium
iodide solution was prepared by dissolving 10 g of
salt (Merck Chemicals, Mumbai,India) in 100 mL of
water. To prepare 1% starch indicator 1 g of soluble
starch (S. d. Fine Chem., Mumbai, India) was made
into paste in water and poured into 100 mL boiling
water, boiled for 1 min and cooled. A stock standard
solution of bromate-bromide equivalent to 1000 g
mL
-1
KBrO
3
containing 10-fold excess of KBr was
prepared by dissolving 100 mg of KBrO
3
and 1 g of
KBr in water and diluting to 100 mL with water in a
calibrated flask. This was diluted appropriately to get
10 and 30 g mL
-1
KBrO
3
solutions for method A and
method B, respectively. A stock solution equivalent to
500 g mL
-1
methyl orange was prepared by
dissolving 58.8 mg of the dye (S. d. Fine Chem.,
Mumbai, India, dye content 85%) in water and
diluting to 100 mL in a calibrated flask, and filtered
using glass wool. It was diluted 10-fold to get 50 g
mL
-1
dye solution for use in method A. stock solution
containing 1000 g mL
-1
indigo carmine was first
prepared by dissolving 111 mg of dye (S. d. Fine
Chem., Mumbai, India, dye content 90 %) in water
and diluting to 100 mL in a calibrated flask, and
filtered. A working concentration of 200 g mL
-1
dye
solution was obtained by 5-fold dilution with water
for method B. A 5 M hydrochloric acid was prepared
by diluting 112 mL of concentrated acid (S. d. Fine
Chem., Mumbai, India, Sp gr 1.18) to 250 mL with
water. This was further diluted to 2M with water.
Pharmaceutical grade MPT certified to be 99.7 %
pure was gifted by Astra - Zeneca, Bangalore, India,
and used as received. A stock standard solution
containing 1 mg mL
-1
drug solution was prepared by
dissolving 250 mg of pure drug in water diluting to
the mark with water in a 250 mL calibrated flask. This
solution was used in titrimetric work and the same
was diluted stepwise to yield working concentrations
of 10 and 30 g mL
-1
for spectrophotometric
investigations.

Methods
Titrimetry
A 10 mL aliquot of pure drug solution containing
2.5-7.5 mg of MPT was accurately measured and
transferred into a 100 mL Erlenmeyer flask. The
solution was acidified by adding 5 mL of 2 M
hydrochloric acid. Ten mL of bromate-bromide
reagent (510
-3
M w. r. t. KBrO
3
) was pipetted into
the flask, the flask was stoppered, the contents mixed
and let stand for 10 min with occasional swirling.
Finally, 5 mL of 10 % potassium iodide solution was
added, and the liberated iodine was titrated against
0.03 M thiosulphate solution using starch as indicator
towards the end point. A blank titration was
performed, and the amount of drug in the measured
aliquot was calculated from the amount of KBrO
3

reacted with drug.

Spectrophotometric method A
Different aliquots (0.5, 1.0.5.0 mL) of
standard 10 g mL
-1
MPT solution were accurately
measured into a series of 10 mL calibrated flasks by
means of a micro burette and the total volume was
adjusted to 5 mL by adding water. To each flask were
added, 2 mL of 5 M hydrochloric acid and 1 mL of
bromate-bromide reagent (10 g mL
-1
w. r. t KBrO
3
)
in succession. The flasks were stoppered immediately,
contents mixed, and allowed to stand for 5 min with
occasional shaking. Lastly, 1 mL of 50 g mL
-1
methyl orange solution was added to each flask, the
volume was diluted to the mark with water, mixed
well and absorbance measured at 520 nm against a
reagent blank after 10 min.

Spectrophotometric method B
Varying aliquots (0.5-5.0 mL) of standard 30 g
mL
-1
MPT solution were accurately transferred into a
INDIAN J CHEM. TECHNOL., J ULY 2006


356
series of 10 mL calibrated flasks by means of a micro
burette, and the total volume was brought to 5 mL by
adding water. Two mL 5 M hydrochloric acid and
1.5 mL of bromate-bromide reagent (30 g mL
-1
w. r.
t KBrO
3
) were added to each flask, the flasks were
immediately stoppered, the contents mixed well and
let stand for 10 min with occasional shaking. Then,
1 mL of 200 g mL
-1
indigo carmine solution was
added to each flask, the volume was completed to the
mark with water, mixed well and the absorbance of
each solution was measured at 610 nm against a
reagent blank after 10 min.
In either method, a standard graph was prepared by
plotting the absorbance as a function of concentration
of MPT. The concentration of the unknown was read
from the calibration graph or deduced from the
respective regression equation derived from the
Beers law data.

Method for tablets
Twenty tablets were weighed and powdered. An
amount of powder equivalent to 100 mg of MPT was
accurately weighed into a 100 mL calibrated flask,
60 mL of water added and shaken for 20 min. Then,
the volume was diluted to the mark with water, mixed
well and filtered using a Whatmann No. 42 filter
paper. A suitable aliquot was then analysed by
titrimetry. The tablet extract (1000 g mL
-1
MPT) was
diluted with water to obtain working concentrations of
10 and 30 g mL
-1
for analysis by spectrophotometric
methods.

Results and Discussion
The acidified solution of bromate and bromide
behaves as an equivalent solution of bromine and has
been widely used for the determination of many
organic and inorganic substances
31,32
. The present
methods make use of oxidising/brominating ability,
and bleaching action of in situ generated bromine.

Method development
Titrimetry
Direct titration of MPT with in situ generated
bromine was not successful. However, the reaction
between the two was found to occur when the two
were allowed to stand for some time, thus enabling
the indirect titrimetric determination of MPT. Hence,
several factors like nature of acid and its
concentration, reaction time, and the excess of reagent
were optimized. Reproducible and stoichiometric
results were obtained when 0.24 to 0.56 M
hydrochloric acid concentration was maintained.
Hence, 0.4 M acid concentration for the
bromination/oxidation step and the iodometric back
titration was used in the assay. Reaction was complete
in 10 min and yielded stoichiometry of 1:1 (MPT :
KBrO
3
), and contact times up to 20 min had no effect
on the stoichiometry of the reaction. A constant
molar-ratio was obtained when excess of reagent was
not more than 2 times the theoretical amount. Under
the optimum conditions, 2.5 - 7.5 mg of MPT could
be determined with good accuracy and precision with
reaction stoichiometry of 1:1.

Spectrophotometric methods
The ability of bromine to effect
oxidation/bromination of MPT and bleach the
colour of methyl orange and indigo carmine dyes
has been used for the indirect spectrophotometric
assay of MPT. In both methods, the drug was
reacted with a measured excess of in situ generated
bromine in acid medium and the unreacted bromine
was determined by reacting with either methyl
orange or indigo carmine followed by absorbance
measurement at 520 or 610 nm. In either method,
the absorbance increased linearly with increasing
concentration of MPT.
MPT, when added in increasing amounts to a fixed
amount of bromine, consumed the latter and there
occurred a concomitant fall in its concentration. When
a fixed amount of either dye was added to decreasing
amounts of bromine, a concomitant increase in the
concentration of dye resulted. This was observed as a
proportional increase in absorbance at the respective

max
with increasing concentration of MPT and Beers
law is obeyed in the concentration range given in
Table 2.
Preliminary experiments were performed to
determine the maximum concentration of each dye
spectrophotometrically, and these were found to be 5
and 20 g mL
-1
for methyl orange and indigo
carmine, respectively. A bromate concentration of 1.0
g mL
-1
(in the presence of excess KBr) was found to
destroy the red colour due to 5 g mL
-1
methyl orange
whereas in the case of 20 g mL
-1
indigo carmine,
4.5 g mL
-1
KBrO
3

was sufficient to bleach the blue
colour in acid conditions. Hence, different amounts of
MPT were reacted with 1.0 mL of 10 g mL
-1
KBrO
3

in method A and 1.5 mL of 30 g mL
-1
KBrO
3
in
method B before determining the residual bromine as
described under the respective procedures.
BASAVAIAH et al.: SENSITIVE BROMATOMETRIC METHODS FOR THE ASSAY OF METAPROLOL TARTRATE


357
Hydrochloric acid was the ideal medium for
oxidation/bromination reaction as well as the
determination of residual bromine by using either dye.
The reaction between MPT and bromine (in situ) was
unaffected when 1.0 -5.0 mL of 5 M hydrochloric
acid was used in about 8 mL. Hence, 1 mL was used
for both steps in the assay procedures. For
quantitative reaction between MPT and bromine (in
situ), a contact time of 10 min was found sufficient in
both methods and constant absorbance readings were
obtained when contact times were extended up to 30
min. The standing time of 5 min was necessary for the
bleaching of dye colour by the residual bromine. The
measured colour was stable for several hours even in
the presence of reaction product.

Quantation parameters
A linear correlation was found between absorbance at

max
and concentration of MPT in the ranges given in
Table 2 in both the methods. The graphs obeyed Beers
law and can be described by the regression equation:
Y =a +bX

(where Y =absorbance; a =intercept; b =slope and X
=concentration in g mL
-1
) obtained by the method
of least squares. Correlation coefficients, intercepts
and slopes for the calibration data are summarized in
Table 2. Sensitivity parameters such as apparent
molar absorptivity and Sandell sensitivity values, and
the limits of detection and quantification are also
presented in Table 2 and speak of the excellent
sensitivity of the proposed methods.

Method validation
Assay precision and accuracy
Intra-day and inter-day precision were assessed
from the results of seven replicate analyses on pure
drug solution. The mean values and the relative
standard deviation (RSD) values for replicate analyses
at three different levels (amounts/concentrations) are
compiled in Table 3. To evaluate the inter-day
precision, anaysis was performed over a period of five
days preparing all solutions afresh each day. The
accuracy of the methods was determined by
calculating the percentage deviation observed in the
analysis of pure drug solution and expressed as the
percent relative error (RE). Table 3 summarises the
intra-day precision and accuracy data for the assay of
MPT in pure drug solution by the proposed methods,
which were within 3%. The inter-day precision was
less than 4%.

Application to analysis in dosage forms
The Indian pharmaceutical industry has at present 4
different brands of tablets in 25, 50 and 100 mg doses.
Three brands of tablets were assayed by the proposed
methods, and the results are summarized in Table 4.
The results obtained were compared with those
obtained by the established UV-spectrophotometric
methods
5
which consisted of the measurement of the
absorbance of tablet extract in 0.1 M HCl at 224 nm.
A close agreement between the results obtained by the
proposed methods and the reference method interms
of accuracy and precision was obtained as found from
the Students t-value and F-value.
Table 3 Intra-day precision and accuracy
Titrimetry Method A Method B
MPT
taken,
mg
MPT
found,
mg
Range,
mg
Relative
error, %
RSD,
%
MPT
taken, g
mL
-1

MPT
found, g
mL
-1

Range, g
mL
-1

Relative
error, %
RSD, % MPT
taken, g
mL
-1

MPT
found, g
mL
-1

Range, g
mL
-1

Relative
error, %
RSD,
%
3.0 3.03 0.12 1.0 0 2.25 1.50 1.48 0.017 1.33 2.41 3.0 2.95 0.028 1.67 2.54
5.0 5.01 0.35 0.20 2.59 3.00 2.92 0.029 2.67 1.35 6.0 5.91 0.093 1.50 1.94
7.0 6.97 0.04 0.43 1.84 4.50 4.40 0.070 2.22 2.36 12.0 11.78 0.049 1.83 2.24
Mean value of seven determinations
RSD.Relative standard deviation
Table 2 Quantitative parameters of spectrophotometric
methods
Parameters Method A Method B
max (nm) 520 610
Beers law limits (g mL
-1
) 0.5 - 5.0 1.5 - 15.0
Molar absorptivity (l mol
-1
cm
-1
) 8.17 10
4
2.70 10
4

Sandell sensitivity (g cm
-2
) 0.0084 0.025
Limit of detection (g mL
-1
) 0.054 0.15
Limit of quantification (g mL
-1
) 0.165 0.47
Regression equation (Y)
Slope (b) 0.11 0.04
Intercept (a) 0.012 -6.7 10
4

Correlation coefficient (r) 0.9989 0.9988
Y=a +bX where Y is the absorbance and X concentration in
g mL
-1
.
INDIAN J CHEM. TECHNOL., J ULY 2006


358

Accuracy and validity of the methods were further
established by performing recovery experiments via
standard-addition technique. To a fixed amount of
drug in tablet powder (pre-analyzed), pure MPT was
added at three different levels and the total was found
by the proposed methods. Each test was repeated
three times. The recovery of pure MPT added to
formulations ranged from 97.60 - 102.50% (Table 5)
indicating that tablet excipients such as talc, starch,
acacia, stearate, alginate, lactose, calcium gluconate
and calcium dihydrogen orthophosphate did not
interfere in the assay procedures.

Conclusions
Three simple, rapid and cost-effective methods for
the assay of metaprolol tartrate in bulk drug and tablet
dosage form have been developed and appropriately
validated. The titrimetric method is applicable over a
micro scale and is independent of the experimental
variables that would often affect the accuracy and

precision. Unlike most of the existing
spectrophotometric methods, the proposed procedures
are free from stringent experimental conditions and
are characterized by long dynamic linear range of
response and high sensitivity, and infact, the methods
are one of the most sensitive ever reported for MPT.
Another significant advantage of the
spectrophotometric methods is that the measurement
is made at longer wavelengths where the interference
from co formulated substances is far less compared to
shorter wavelengths used in most currently available
procedures. In addition, all the three methods have
demonstrated to be fairly accurate and precise, and
may be used as advantageous alternatives in industrial
quality control laboratories.

Acknowledgements
The authors wish to express their gratitude to the
Quality Control Manger, Astra - Zeneca,
Bangalore, India for providing pure metaprolol
Table 4 Assay results of dosage forms
Percent found* SD Formulation brand
name **
Nominal amount
(mg/tablet )
Tirimetry Method A Method B Reference method
Betaloc 50 g
100.10 1.41
t =0.79
F =3.27
101.20 1.39
t =0.80
F =3.17
99.98 0.87
t =1.28
F =1.24

100.65 0.78




100 g
99.89 1.62
t =0.48
F =2.84
101.30 1.42
t =1.35
F =2.18
102.30 0.93
t =3.38
F =1.06

100.28 0.96


Metolar

100 g
97.98 1.44
t =1.84
F =1.81
98.50 1.33
t =1.24
F =1.54
98.14 1.77
t =1.45
F =2.74

99.44 1.07


Metapro


50 g
101.77 1.85
t =1.47
F =4.42
99.20 1.73
t =1.57
F =3.86
102.50 1.39
t =2.78
F =2.49

100.50 0.88
* Mean value of five determinations
**Marketed by: a. AstraZeneca
b. cipla
c. Microvascular
Tabulated t-value at 95 % confidence level is 2.77
Tabulated F-value at 95 % confidence level is 6.39
Table 5 Results of recovery studies
Titrimetry Method A Method B
Preparation
studies
Amount
of drug in
tablet, mg
Amount of
pure drug
added, mg
Total
found,
mg
Recovery
of pure
drug, %
Amount
of drug in
tablet, g
Amount of
pure drug
added, g
Total
found,
g
Recovery
of pure
drug, %
Amount
of drug in
tablet, g
Amount of
pure drug
added, g
Total
found,
g
Recovery
of pure
drug, %
3.912 1.0 4.92 101.00 9.85 10.00 20.10 102.50 24.53 30.0 53.81 97.60
3.912 2.0 5.93 100.75 9.85 20.00 29.90 100.25 24.53 60.0 85.37 101.40
Metolar
3.912 3.0 6.98 102.00 9.85 30.00 39.55 99.00 24.53 120.0 143.65 99.27
* Mean value of three determinations
BASAVAIAH et al.: SENSITIVE BROMATOMETRIC METHODS FOR THE ASSAY OF METAPROLOL TARTRATE


359
tartrate as gift. Two of the authors (BCS & VRK)
thank the authorities of the University of Mysore,
Mysore, for research facilities. VRK is thankful to
the Principal Secretary, Department of Health and
Family Welfare, Govt. of Karnataka, Bangalore, for
permission.

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