Impurities

Source of impurities:
1. During synthesis
2. During manufacturing
3. During storage

Impurities
Classification of chemicals :
1. Commercial chemicals
2. Pure chemicals
3. Analytical chemicals
4. Pharmaceutical chemicals

Pharmacopoeia

A description of the article

Tests for identity
Physical constants
Quantitative assay
Limit test Storage conditions
official = obey the requirement

Pharmacopoeia
British pharmacopoeia (BP)
European pharmacopoeia (Eu.Ph)
United state pharmacopoeia (USP)

Limit test
They are quantitative or semi-quantitative
test designed to identify or control small
quantities of impurity ,these test should be
specific and sensitive

Limit test
Type:
1. Comparison method
2. Quantitative determination
3. Test in which there is no visible
reaction

Limit test
General principle
If the sample is lighter than the
standard solution then it is within the
pharmacopeial limit (accepted)
If the sample is darker/heavier than the
standard solution then it is above the
pharmacopeial limit (rejected)

Limit test
NESSLER cylinder
(appendix VII A127)
clear glasses with normal capacity 50ml, the
overall height is about 15cm, the external
height to the 50ml mark 11.0 to 12.4 cm ,the
thickness of the wall 1.0 to 1.5 mm and the
thickness of the base 1.0 to 3.0mm the
external heights to the 50 mark of cylinders
used to test must not differ by more than 1
mm

Limit test
General precaution
1.
2.
3.
4.
5.

The liquid used must be clean and filtered if

necessary
The Nessler cylinder must be made of colorless
glass and of the same inner diameter
Detecting opalescence or color development must
be performed in daylight
When comparing turbidity it should be done
against black background
When comparing color it should be done against
white background

Limit test

Limit Test for Ammonium

Principle
NH4+ + K2HgI4

0.3ml Nessler reagent

dd dist. water to 50 ml

5ml sample solution

NH2Hg2I3

0.3ml Nessler reagent

Add dis. water to 50 ml
10ml of standard NH4+ (1ppm)
+5ml H2O

Limit Test for Chloride

:Principle
Cl- + AgNO3AgCl
1ml AgNO3

Dist. H2O to 50 ml
1ml HNO3
15ml sample

1ml AgNO3
Dist. H2O to 50ml
1ml HNO3
10ml St Cl- (5ppm)
5ml H2O+

Limit Test of Sulphate

:Principle
SO4-2 + BaCl2

BaSO4

Complete1.5ml
volume
ethanolic
with Dil.water
SO4standard
to 50ml
15ml
water
&MIX by rotation
wait
minute
Mixfor
by 1
rotation
1ml 25%BaCl2

15ml Standard

Add 0.5ml acetic acid(5M

15ml sample

Limit Test for Iron

Principle:
Fe+3 + NH4SCN
Procedure:
5ml NH4SCN
H2O to 50ml
5ml HNO3
10ml sample

Why we use nitric acid?

Fe(SCN)3
5ml NH4SCN
H2O to 50ml
5ml HNO3
10ml standard

Limit Test of Calcium

Principle:
Ca+2 + (NH4)2C2O4
Procedure

CaC2O4

0.2ml alcoholic calcium stander(100ppm)

1ml ammonium oxalate

1 MIN

10ml calcium stander

)10ppm(

2ml calcium stander

)100ppm(

5 ml dist water

20 ml dist water
Pipette 15 ml

1ml acetic acid

to 50ml with
dist water

Aspirin
Limit Test of Salicylic Acid

0.05 ml FeCl3

to 50ml H2O

15 ml iced H2O
0.1ml acetic acid

0.1gm sample
5ml ethanol

ml FeCl3 0.05
to 50ml H2O
ml iced H2O 15
0.1ml acetic acid
1ml salicylic acid

4ml ethanol

Limit Test of Heavy Metal

Principle:
Pb+2 +NaS

1.2ml
thioacetamide
Sample
preparation

mix

2.5g aspirin
2ml acetate
bufferin 30ml
dissolve
12ml sample
acetone then
complete to 50
ml with H2O

PbS
1.2ml thioacetamide

mix

2ml acetate buffer

10ml standard Pb
2ml sample

Quantitative Limit Test

Determination of lead concentration in a
sample of heavy metals
Primary solution

Auxiliary solution
3ml standard

4ml standard

2ml standard
5drops thioacetmide

1 ml NH4OH

ml sample

5drops thioacetmide

1 ml NH4OH
1ml sample

5ml standard

Non Aqueous Acid-Base Titration

Main reasons for non aqueous titration :
Solubility: many organic compound (acid
or base) sparingly soluble in water but
readily soluble in organic solvent
Too weak acid or base : they didnt give
sharp end point in aqueous titration but
can titrated accurately in suitable non
aqueous solvent

Non Aqueous Acid-Base Titration

Titration solvents

Protic

Inert neutral substance as

:benzene , chloroform and
Aprotic
hydrocarbon

Non Aqueous Acid-Base Titration

Protic solvent :
Amphiprotic :it self dissociation (autoprotolysis)

which process acidic and basic properties

e,g:H2O,AcOH, ALCOHOL and liquid ammonia
2H2O
H3O+ + OH2C2H5OH
C2H5OH2+ +C2H5O-

Protogenic: they have stronger acidic than basic

properties (more acidic than water)

E,g: CH3COOH & H2SO4

B + CH3COOH
BH + + CH3COO-

Non Aqueous Acid-Base Titration

Protic solvent :
Protophilic : basic substance and react with acidic
solute with the formation of solvated proton and
conjugated base of acid (more basic than water)
E,g :ether ,ketone & amine
HB +S
HS+ + B-

Non Aqueous Acid-Base Titration

Type of Titrant:
Perchloric acid (HClO4)Used for titration in acetic acid
media , it is commonly use for titration of weak media
Alkali metal bases: alcoholic potassium hydroxide or
alcoholic sodium hydroxide they used for titration of
moderately weak acid
Quaternary ammonium hydroxide: tetra butyl ammonium
hydroxide the most widely used titrant for acid in non
aqueous titration

Non Aqueous Acid-Base Titration

Advantage of These Titrant
Excellent potentiometric curve using
ordinary glass or calomel electrode

The salt formed from this titration are

soluble in the solvent commonly used

Titration of Adrenaline
Principle
HClO4 + CH3COOH
+ CH3COOH

+ HClO4

CH3COOH2+ + ClO4CH3COO- +

+ ClO4-

Titration of Adrenaline
:Volumetric
1.
2.
3.
4.

In dry conical flask weigh 0.2g adrenaline

Add 25ml glacial acetic acid
End
when
blue
Onepoint
drop crystal
violetgreenish
indicator
Titrate against perchloric acid

appear

Poteatiometric
5. In dry beaker 0.2g adrenaline
Add 0.5ml
until
near the E.P add 0.1ml
6. 25ml glecial
acetic
acid
7. Titate against perchloric acid

Titration of Adrenaline
Calculation
From the equivalent factor each ml of perchloric acid react
with 0.01832 of C9H13NO3
F= (molecular weight of sample*molarities of standard)
1000

Theoretical (equivalent point)

1ml of 0.1M HClO4

the weighted
amount of
0.2g adrenaline

X ml
sample
X= equivalent

0.01832g adrenaline

point

Titration of Adrenaline
Calculation
%of deviation= end point from the
graph*100
equivalent point
Limitation 101% -98,5%

Titration of Phenobarbitals
Principle

Add 3 drop of ph.ph to the

alcohol then add sufficient
amount of NaOH (0.02
or0.1N) TO produce PINK
Volumetric titration
COLOR

Titration of Phenobarbitals

1.
2.
3.
4.

In dry conical flask weight 0.5g Phenobarbital

Add 40ml neutralized alcohol
End
when fine pink color appear
Add point
20 ml water
Titrate against 0.1N NaOH using ph.ph as indicator

Potentiometric titration

1.
2.
3.
4.

In a dry beaker weight 0.5g Phenobarbital

Add 40ml neutralized alcohol
Add 20 ml water
Titrate against 0.1N NaOH

Titration of Adrenaline
Calculation
1ml 0.1N NaOH

23.22mg Phenobarbitals

Limitation 101% -98,5%

potentiometric curve

Safety
Crystal violet
may cause cancer. Severe eye irritant. Harmful by inhalation,
ingestion and through skin contact.

Perchloric acid
It is very corrosive to skin and eyes, It can also ignite or explode upon
contact with organic material such as cloth or wood also Causes
hypothyroidism digestive and respiratory tract burns& it is Corrosive
to metal

glacial acetic acid

This material is strongly corrosive and causes serious
burns. Very harmful if swallowed. Lachrymator