A Text Book Of

PHARMACEUTICAL
ANALYSIS
As Per PCI Regulations

FIRST YEAR B. PHARM.

Semester I

Dr. Puspendra Kumar

M. Pharm., Ph.D.
Associate Professor
KIET School of Pharmacy,
KIET Group of Institutions, Ghaziabad

Price ` 160.00

N4007
Pharmaceutical Analysis ISBN 978-93-86700-36-0
Second Edition : April 2018
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 Dr. Shivesh. Jha
Professor
Dept. of Pharm. Sci. & Tech.
Birla Institute of Technology
Mesra, Ranchi

Foreword

Pharmaceutical analysis is backbone of drug industries and highly useful to

standardize the modern medicinal agents. Basic analytical technique includes acid base
titrations, redox titrations, precipitation titrations, complexometric titrations,
gravimetric analysis, potentiometry, polarography and conductometric analysis. Hence,
presenting all the basic and significant aspects of the vast area of knowledge within the
limited space is indeed a stupendous job which Dr. Puspendra Kumar has been able to
achieve with a fair degree of success in a commendable manner.

This book presents a rich text material which provides background information of
various topics. Diagrammatic representation of the methodologies will be highly
beneficial for the readers. Examples are cited in a simple manner which enhances the
understanding of the topics. Dr. Kumar has taken great effort in compiling
fundamentals of analysis in very simple and organized manner; which will be supportive
in developing basics of students.

I am sure; this book will be a good and useful aid to those involved in teaching and
learning of pharmaceutical analysis. I wish him for success and congratulate him for his
excellent efforts.

With Best Wishes

Dr. Shivesh Jha

Preface
It gives me immense pleasure to present to pharmacy students my book entitled
“Pharmaceutical Analysis”. Writing a book is inspiring, often exciting, and sometimes very
challenging work.

Pharmaceutical analysis plays a vital role in evaluation of various drug(s)/ compound(s)

sample. Analysis of the compounds starts from basic analytical tools i.e. calibration of the
glasswares, handling of the analytical balance, various titration methods, electrochemical
methods etc. Thus, without basic analytical tools further advanced study is tedious and costly.

This book mainly guides students to get knowledge about basics of pharmaceutical
analysis. All the contents are discussed in detail and suitable examples are explained
whenever required. This book is highly useful for understanding of principle(s) involved in
various volumetric methods and covers almost each category of volumetric analysis in a
simplest way. Methodologies of various techniques are represented by diagrams/figure(s) for
better understanding. The book contains calculations and important questions related to the
topics to fulfill the requirements of students.

I am grateful to Dr. Shivesh Jha for his constant encouragement and suggestions given
during completion of this book.

I record my sincere thanks to Dr. Jaya Dwivedi, Dr. Jagannath Sahoo, Dr. Sanjar Alam,
Dr. Swapnil Sharma, Dr. Sunil Kumar Dubey, Dr. Avijit Mazumdar, Dr. Jainendra Jain,
Dr. L. Baskar, Dr. Shekhar Verma, Dr. Rikeshwer, Dr. Abhishek for constant encouragement
and suggestions to write this book.

I thank my wife Mrs. Durgawati Patel for her constant support to review the content of
this book and moral support. I am thankful to my seniors, friends and students who gave me
suggestions whenever I asked for betterment of this book.

I appreciate the co-operation and interest taken by Publisher Shri Dinesh Furia,
Shri Jignesh Furia and Mr. Amit Jha, Mrs. Roshan Khan of Nirali Prakashan, Pune in bringing
out this book.

I will be grateful to all the teachers and students who will be kind enough to point out
my mistakes that have escaped my attention. Suggestions for future improvement are always
welcome.

Dr. Puspendra Kumar

Syllabus
UNIT - I [10 Hours]
(a) Pharmaceutical analysis: Definition and scope.
(i) Different techniques of analysis.
(ii) Methods of expressing concentration.
(iii) Primary and secondary standards.
(iv) Preparation and standardization of various molar and normal solutions - Oxalic acid,
sodium hydroxide, hydrochloric acid, sodium thiosulphate, sulphuric acid, potassium
permanganate and ceric ammonium sulphate.
(b) Errors: Sources of errors, types of errors, methods of minimizing errors, accuracy,
precision and significant figures
(c) Pharmacopoeia, Sources of impurities in medicinal agents, limit tests.
UNIT - II [10 Hours]
• Acid base titration: Theories of acid base indicators, classification of acid base titrations
and theory involved in titrations of strong, weak, and very weak acids and bases,
neutralization curves.
• Non-aqueous titration: Solvents, acidimetry and alkalimetry titration and estimation of
Sodium benzoate and Ephedrine HCl.
UNIT - III [10 Hours]
• Precipitation titrations: Mohr’s method, Volhard’s, Modified Volhard’s, Fajans method,
estimation of sodium chloride.
• Complexometric titration: Classification, metal ion indicators, masking and demasking
reagents, estimation of magnesium sulphate and calcium gluconate.
• Gravimetry: Principle and steps involved in gravimetric analysis, Purity of the precipitate,
Co-precipitation and post precipitation, Estimation of barium sulphate.
• Basic Principles, methods and application of diazotisation titration.
UNIT - IV [08 Hours]
Redox titrations
(a) Concepts of oxidation and reduction
(b) Types of redox titrations (Principles and applications)
Cerimetry, Iodimetry, Iodometry, Bromatometry, Dichrometry, Titration with
potassium iodate.
UNIT - V [07 Hours]
Electrochemical methods of analysis:
• Conductometry: Introduction, Conductivity cell, Conductometric titrations, applications.
• Potentiometry: Electrochemical cell, construction and working of reference (Standard
hydrogen, silver chloride electrode and calomel electrode) and indicator electrodes
(metal electrodes and glass electrode), methods to determine end point of
potentiometric titration and applications.
• Polarography: Principle, Ilkovic equation, construction and working of dropping mercury
electrode and rotating platinum electrode, applications.
,,,
Contents
UNIT I
1. Pharmaceutical Analysis 1.1 - 1.38
1.1 Definition 1.1
1.1.1 Types of Analytical Chemistry 1.2
1.1.2 Steps in Chemical Analysis 1.2
1.1.3 Factors Affecting the Choice of Analytical Technique 1.3
1.1.4 Classification of Pharmaceutical Analysis Laboratories 1.4
1.1.5 Scope of Analytical Chemistry 1.4
1.2 Different Techniques of Analysis 1.5
1.3 Methods of Expressing Concentration 1.5
1.4 Primary and Secondary Standard Substances 1.8
1.4.1 Primary Standard Substances 1.8
1.4.2 Secondary Standard Substances 1.10
1.5 Preparation and Standardization of Various Molar and Normal Solutions 1.10
1.6 Errors 1.22
1.6.1 Sources of Errors 1.23
1.6.2 Types of Errors 1.23
1.6.3 Methods of Minimizing Errors 1.25
1.6.4 Accuracy and Precision 1.25
1.6.5 Significant Figures 1.27
1.7 Pharmacopoeia 1.28
1.8 Sources of Impurities in Medicinal Agents 1.29
1.9 Limit Tests 1.30
• Questions 1.36
UNIT II
2. Acid Base Titrations 2.1 - 2.28
2.1 Introduction 2.1
2.2 Theories of Acid Base Titrations 2.2
2.3 Law of Mass Action 2.3
2.4 Role of Solvents 2.4
2.5 Ionization 2.6
2.6 Relative Strength of Acid and Bases 2.7
2.7 pH and pOH 2.8
2.8 Ionic Product of Water 2.9
2.9 Hydrolysis of Salts 2.10
2.10 Henderson Hesselbach Equation 2.12
2.11 Buffer Solution 2.12
2.12 Classification of Acid Base Titrations 2.15
2.13 Theories of Indicators 2.23
2.14 Indicators of Acid Base Titrations 2.24
• Questions 2.26
3. Non-aqueous Titrations 3.1 - 3.10
3.1 Solvents 3.1
3.2 Types of Solvents in Non-aqueous Titrations 3.2
3.3 Levelling Effect 3.3
3.4 Acidimetry and Alkalimetry Titration 3.4
3.5 Indicators 3.4
3.6 Estimation of Sodium Benzoate 3.7
3.7 Estimation of Ephedrine HCl 3.8
• Questions 3.10
 UNIT III
4. Precipitation Titrations 4.1 - 4.18
4.1 Precipitation Reaction 4.1
4.2 Solubility Products 4.2
4.3 Effect on Solubility of Precipitate 4.3
4.4 Argentometric Titrations 4.4
4.5 Thiocyanatometric Titrations 4.7
4.6 Mercurometric Titrations 4.7
4.7 Gay Lussac's Method 4.9
4.8 Mohr's Method 4.10
4.9 Volhard’s Method 4.11
4.10 Fajan's Method 4.12
4.11 Estimation of Sodium Chloride 4.14
• Questions 4.16

5. Complexometric Titrations 5.1 - 5.26

5.1 Principle 5.1
5.2 Complexing Agents 5.2
5.3 Masking and Demasking Agents 5.3
5.3.1 Masking Agents 5.4
5.3.2 Demasking 5.5
5.4 Indicators 5.7
5.5 Instrumental Methods for End Point Detection in Complexometry 5.9
5.6 Types of Complexometric Titrations 5.10
5.7 Preparation and Standardization of 0.05 m Disodium Edetate Solution 5.11
5.8 Determination of Calcium Gluconate 5.14
5.9 Determination of Magnesium Sulphate 5.16
5.9 Assay of Potassium Alum 5.19
5.10 Determination of Hardness of Water 5.21
• Questions 5.24
6. Gravimetric Analysis 6.1 - 6.12
6.1 Introduction 6.1
6.2 Precipitation Techniques 6.2
6.3 Colloidal Precipitates 6.2
6.4 Supersaturation 6.4
6.5 Co-precipitation 6.5
6.6 Gravimetric Methodology 6.5
6.7 Filter Papers 6.8
6.8 Crucibles 6.8
6.9 Thermogravimetric Analysis (TGA) 6.9
6.10 Organic Precipitants 6.10
6.11 Estimation of Barium Sulphate 6.10
• Questions 6.11
7. Diazotization Titration 7.1 - 7.4
7.1 Principle 7.1
7.2 Types of Diazotization Titrations 7.2
7.3 Methododology 7.2
7.4 Conditions for the Diazotization Titration 7.3
7.5 Advantages and Disadvantages 7.3
7.6 Applications of Diazotization Titration 7.4
• Questions 7.4
 UNIT IV
8. Redox Titrations 8.1 - 8.22
8.1 Introduction 8.1
8.2 Redox Reactions 8.2
8.3 Oxidation Number or Oxidation State (OS) 8.2
8.4 Balancing Simple Redox Reactions 8.3
8.5 Strength and Equivalent Weights of Oxidizing and Reducing Agents 8.3
8.6 Theory of Redox Titrations 8.4
8.7 Redox Indicators 8.5
8.7.1 Types of Indicators 8.5
8.8 Cell Representations 8.6
8.9 Measurement of Electrode Potential 8.6
8.10 Oxidation Reduction Curves 8.7
8.10.1 Cerimetric Titration 8.8
8.11 Iodimetry and Iodometry 8.11
8.12 Bromatometry 8.13
8.13 Dichrometry 8.13
8.14 Titration with Potassium Iodate 8.14
8.15 Some Common Oxidants and Reductants 8.15
8.16 Preparation and Standardisation of 0.1 N KMNO4 Solution 8.15
8.17 Assay of Ferrous Sulphate 8.17
8.18 Assay of Copper Sulphate 8.19
• Questions 8.20

UNIT V
9. Electrochemical Methods of Analysis 9.1 - 9.18
9.1 Conductometry 9.1
9.1.1 Introduction 9.1
9.1.2 Fundamentals of Conductometry 9.2
9.1.3 Instrumentation 9.3
9.1.4 Types of Conductometric Titrations 9.4
9.1.5 Advantages and Disadvantages of Conductometric Titrations 9.7
9.1.6 Applications of Conductometry 9.7
9.2 Potentiometry 9.7
9.2.1 Introduction 9.7
9.2.2 Electrochemical Cell 9.8
9.2.3 Reference Electrodes 9.9
9.2.4 Indicator Electrodes 9.12
9.2.5 Instrumentation 9.13
9.2.6 Types of Potentiometric Titrations 9.14
9.2.7 Applications and Advantages of Potentiometric Titrations 9.15
9.3 Polarography 9.15
9.3.1 Principle 9.15
9.3.2 Ilkovic Equation 9.15
9.3.3 Dropping Mercury Electrode (DME) 9.16
9.3.4 Rotating Platinum Electrode (RPE) 9.17
9.3.5 Applications and Advantages of Polarography 9.17
• Questions 9.17
• Index I.1 - I.4
• Appendix A.1 - A.4
,,,
 FUNDAMENTAL CONCEPTS

Preliminaries and Definitions:

1. Volumetric or Titrimetric Analysis: It consists of determination of volume of solution of
accurately known concentration required to react completely with the solution of
substance to be determined.
2. Standard Solution: The solution of accurately known concentration is called as the
standard solution.
3. Standardization: Standardization is the method of analysis to determine and ensure the
claimed quantity of the compounds or chemicals.
4. Titrate/Titrand: The solution of unknown concentration and the substance being
titrated is called titrate.
5. Titrant: The solution of known concentration is used in titration (usually added from
burette).
6. Equivalence point of stoichiometric end point: The point at which the reaction
between titrant and titrate (titrand) is just completed.
7. End-point: The point at which the reaction between titrant and titrate (titrand) is
showing some changes in terms of colour, pH etc. during experiment.
8. Indicator: It is an auxiliary substance which shows clear viral change after the reaction
between titrant and titrates is particularly complete.
9. Titration Error: In practice, usually there is very small difference between theoretical
end-point and actual end-point. This is called as titration error.
10. True Value: Actual or correct value is considered as true value. True values are known
only when we count objects or when a quantity is assigned a particular value. In other
cases the true value of a quantity is never known.
11. Standard Value: Standard values are representative values based on the experience
record of the process. If an expert using a suitable method and a good quality apparatus
carefully determine the percentage value, then it is called standard value.
12. Observed Value: The observed value is the value truly measured as the test is performed
in the laboratory.
13. Error: The difference between the true value or standard value and observed value is
called error.
,,,
 UNIT I

Chapter ... 1
PHARMACEUTICAL ANALYSIS

♦ LEARNING OBJECTIVES ♦
• The course intends to impart knowledge of the basic analytical techniques involved in
determining unknown concentrations of different constituents present in solutions or solids
using volumetric titrations or gravimetric methods.
• To study the preliminaries and definitions used in analysis.
• To study the accuracy and precision parameters and minimization of errors during analytical
experiments.

OUTCOMES
On satisfying the requirements of this course, students will have the knowledge and skills
to:
• Understand that all measurements involve errors and that the analytical procedure is only
as accurate as the least accurate measurement.
• Understand that for each technique the sources and magnitudes of errors can be
identified and quantified (If possible); and finally errors can be reduced upto great extent.
• Understand that the magnitude of the error in the analysis can be reflected using the
correct significant figures when reporting results.
• Have complete knowledge of basic terms like molarity, molality, normality, weight
percentage calculation and applications based on them.
1.1 DEFINITION
Pharmaceutical analysis or chemical analysis is 'a technique to identify and/or quantify
any sample, substance, compound by using manual, chemical or instrumental techniques by
qualitative or quantitative method(s)'. Analytical chemistry is apprehensive with the theory
and practice of techniques used to determine the composition of substance(s). Analytical
chemistry is very broad and squeezes a wide range of techniques. Chemical analysis is
applied in daily life i.e. soaps and detergents act as emulsifiers to surround dirt and grime so
it can be washed away from clothing, dishes and our bodies. Analytical chemistry can be
classified into qualitative and quantitative analysis.
(1.1)
Pharmaceutical Analysis 1.2 Pharmaceutical Analysis

1.1.1 Types of Analytical Chemistry

1. Qualitative Analysis: Completely unknown sample is analysed to determine the
presence or absence of the particular substance(s) in the sample, and the technique is
known as qualitative analysis. Qualitative analysis is based on either present or absent
phenomenon. Identification of the compounds or substances takes place in this
technique.
Example: Phenolphthalein indicator gives light pink colour in alkaline medium; light pink
colour in the alkaline solution will be either present or absent. The technique is
qualitative analysis because we are not determining the intensity of colour present.
2. Quantitative Analysis: Determination of the quantity in numbers, weight, length or any
other measurement parameter is carried out under quantitative analysis. Specified
components are quantified in the sample by using quantitative methods. Various
quantitative methods are available to determine the samples(s). i.e.: Titrimetry, volumetry,
gravimetry, thermal, electro-chemical, spectral analysis etc.
Example: Assay of NaCl is carried out by volumetric method and the accurate
percentage purity of the given sample is determined by volumetric analysis.
1.1.2 Steps in Chemical Analysis
1. Sampling
An analyst has to determine the nature of a large quantity of substances(s). In ideal
condition analyst should analyze every part of the substance(s) to get the accurate result, but
it is not possible every time. So, according to the physical nature and size of the substance(s)
available sampling is carried out.
2. Sample preparation
Sample preparation includes the dealing of the samples prior to its analysis i.e. reduction
of the particle size, mixing of the samples to get homogeneity, drying of the samples,
determination of quantity of the sample in terms of weight or volume etc.
3. Processing of sample for analysis
Accurate and above selected sample(s) are processed to carry out the analysis
i.e. heating, fusion or ignition of the sample(s), use of the solvent(s) to dissolve the sample(s),
dilution of the sample(s) etc. In second step of the sample processing the prepared sample(s)
are treated by suitable method to purify, to get better and accurate results i.e. filtration,
solvent extraction, ion exchange methods, chromatographic separations etc.
4. Selection of analytical technique(s)
Selection of appropriate method was done by the analyst, and basis of the selection is
nature of the sample and required output. Various analytical methods are available for
analysis of the samples. i.e. volumetric, gravimetric, spectroscopic, electro-chemical etc.
5. Analysis of sample by selected technique
Appropriate analytical method is selected and samples are analysed by selected method
to get the result(s). Analysis of the sample involves calibration, optimization, standardization
 Pharmaceutical Analysis

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