PHARMACEUTICAL ANALYSIS (MODULE 2)
Aqueous and Non-aqueous Titrimetric
Analysis
1. Acidimetry – acidic titrant with basic
analyte
A. Direct Titration
B. Residual titration
C. Nitrogen Determination by Kjeldahl
Method
2. Alkalimetry - basic titrant with acidic
analyte
A. Direct Titration
B. Residual titration
Direct Titration
- is conducted by introducing a standard
acid solution gradually from a buret into a
solution a solution of the base being
assayed until chemically equivalent
amounts of each have reacted as shown
by some change in properties of the
mixture.
Alkalimetry in Aqueous Medium
Alkalimetry - basic titrant with acidic
analyte
A. Direct Titration
B. Residual titration
Direct Titration
- is conducted by introducing a standard
base solution gradually from a buret into a
solution a solution of the acid being
assayed until chemically equivalent
amounts of each have reacted as shown
by some change in properties of the
mixture.
Residual Titration
- Residual titration methods are used
whenever direct titration methods
are not practicable.
Residual Titration
- Residual titration is carried out by
dissolving the substance under
examination in an accurately measured
quantity of standard solution known to be
in excess and titrating the excess of the
latter with another standard solution.
- is used whenever the end point of a
direct titration deviates appreciably from
the stoichiometric points for the following
reasons;
● when the reaction proceeds slowly
Nitrogen Determination by Kjeldahl
Method
- the Kjeldahl method first came into
existence in 1883 and was developed by a
Danish chemist named Johan Kjeldahl.
This method was specifically developed
for determining the nitrogen contents in
organic and inorganic substances.
NON AQUEOUS TITRIMETRIC
ANALYSIS
- characteristics of medicinal substances
that this method can be used:
- for poorly soluble & weakly reactive
substances in water
-Precautions observed in the use of this
process:
- moisture is to be avoided in using
non-aqueous procedures, since H2O
being weakly basic would compete with
the weak nitrogen for the HClO4 and the
sharpness of the end point would be lost.
Acidimetry: analyte : free base titrant :
acid

Aqueous Non-
aqueous

Vs HCl Perchloric
H2SO4 acid in
glacial HAc

Perchloric
acid

1 std Na2CO3 K biphthalate

2 std NaOH

Examples:
NaOH,
Direct Na2CO3
NaHCO3,
Na salicylate
Methacholin
ZnO, e Cl
Residual tartrate,
methenamin
e

Alkalimetry: analyte : acid titrant : base

Aqueous Non-aqueou
s

VS NaOH Na
methoxide in
MtOH or
Toluene

1 std K biphthalate -----

2 std HCl &

H2SO4 ----

Eg.
H3PO4,
Direct H3BO3,
HCl
Phenytoin

Residual ASA
 PHARMACEUTICAL ANALYSIS 1 (MODULE 3)

Reactions involving Combination of 3. Adsorption indicators

Ions Examples:
1. Volumetric precipitation DCF (Dichlorofluorescein),
Volhard Method Eosin Y TS,
Mohr Method TEE (Tetrabromophenolpthalein Ethyl
Fajans Method ester) TS
Gay Lussac’s method
Liebig Method Standard Solutions
- The standard solutions employed in
2. Complexation/ Chelometry reaction the official assays by precipitation
methods are:
Volumetric Precipitation 0.1 N silver nitrate
- In volumetric precipitimetry a class of 0.1 N ammonium thiocyanate
reactions is dealt with that require the
formation of relatively insoluble 3.2 Complexation
substances or precipitates to cause the - Vs: Ca EDTA (hexa dentate ligand)
reactions to go to sufficient completion to - 1 std: CaCO3
be quantitative in nature. Indicators:
hydroxynaphthol blue,
Determination of the End Point dithizone, eriochrome black
- The end point of a reaction in analysis by
precipitation methods may be determined MASKING
in the following ways: - metal detection in the presence of
1. Cessation of precipitation or the another metal
appearance of a turbidity
2. Use of internal indicators
3. Instrumental methods, i.e.
potentiometric or amperometric

Indicators
1. Ferric ammonium sulfate TS
- This indicator is used both in direct and
residual titration employing standard
ammonium thiocyanate solution.

2. Potassium chromate
- It forms a red precipitate of silver
chromate which is seen against the
background of white silver chloride