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Table of Contents
Preface to the Second Edition
Abbreviations
Symbols and Units
Constants
Greek alphabet
1 Introduction to Pharmaceutical Analytical Chemistry
1.1 Introduction
1.2 Pharmaceutical Analytical Chemistry
1.3 This Textbook
2 Marketing Authorizations, Pharmaceutical Manufacturing,
and International Pharmacopoeias
2.1 Introduction
2.2 Marketing Authorization and Industrial Production
2.3 Pharmacopoeias
2.4 Life Time of Pharmaceutical Preparations and
Ingredients
3 Fundamentals of Bases, Acids, Solubility, Polarity, Partition,
and Stereochemistry
3.1 Acids, Bases, pH, and pK a
3.2 Buffers
3.3 Acid and Base Properties of Drug Substances
3.4 Distribution Between Phases
3.5 Stereoisomers
3.6 Active Pharmaceutical Ingredients – A Few Examples
3.7 Stability of Drug Substances
4 Fundamentals of Pharmaceutical Analytical Chemistry
4.1 Pharmaceutical Analytical Chemistry
 4.2 How to Specify Quantities, Concentrations, and
Compositions of Mixtures
4.3 Laboratory Equipment
4.4 How to Make Solutions and Dilutions
4.5 Errors, Accuracy, and Precision
4.6 Statistical Tests
4.7 Linear Regression Analysis
4.8 How to Present an Analytical Result
4.9 Additional Words and Terms
5 Titration
5.1 Introduction
5.2 Potentiometric Titration and Electrodes
5.3 Aqueous Acid–Base Titrations
5.4 Titration in Non‐aqueous Solvents
5.5 Redox Titrations
5.6 Alternative Principles of Titration
6 Introduction to Spectroscopic Methods
6.1 Electromagnetic Radiation
6.2 Molecules and Absorption of Electromagnetic Radiation
6.3 Absorbing Structures – Chromophores
6.4 Fluorescence
6.5 Atoms and Electromagnetic Radiation
7 UV‐Vis Spectrophotometry
7.1 Areas of Use
7.2 Quantitation
7.3 Absorbance Dependence on Measurement Conditions
7.4 Identification
7.5 Instrumentation
7.6 Practical Work and Method Development
7.7 Test of Spectrophotometers
 7.8 Fluorimetry
8 IR Spectrophotometry
8.1 IR Spectrophotometry
8.2 Instrumentation
8.3 Recording by Transmission, Diffuse Reflectance, and
Attenuated Total Reflection
8.4 Instrument Calibration
8.5 NIR Spectrophotometry
9 Atomic Spectrometry
9.1 Applications of Atomic Spectrometry
9.2 Atomic Absorption Spectrometry (AAS)
9.3 AAS Instrumentation
9.4 AAS Practical Work and Method Development
9.5 Atomic Emission Spectrometry (AES)
9.6 Flame Photometry
9.7 Inductively Coupled Plasma Emission Spectrometry
9.8 Inductively Coupled Plasma Mass Spectrometry
10 Introduction to Chromatography
10.1 Introduction
10.2 General Principles
10.3 Retention
10.4 Efficiency
10.5 Selectivity
10.6 Resolution
10.7 Peak Symmetry
10.8 The Dynamics of Chromatography
11 Separation Principles in Liquid Chromatography
11.1 Introduction
11.2 Reversed‐Phase Chromatography
11.3 Ion‐Pair Chromatography
 11.4 Normal‐Phase Chromatography
11.5 Thin‐Layer Chromatography
11.6 Hydrophilic Interaction Chromatography
11.7 Ion Exchange Chromatography
11.8 Size Exclusion Chromatography
11.9 Chiral Separations
11.10 Supercritical Fluid Chromatography
12 High Performance Liquid Chromatography
12.1 Introduction
12.2 The Column
12.3 Scaling Between Columns
12.4 Pumps
12.5 Injectors
12.6 Detectors
12.7 Mobile Phases
12.8 Solvents for Sample Preparation
13 Gas Chromatography
13.1 Introduction
13.2 Basic Principle
13.3 Instrumentation
13.4 Carrier Gas
13.5 Stationary Phases
13.6 Retention
13.7 Columns
13.8 Injection
13.9 Detectors
13.10 Derivatization
14 Electrophoretic Methods
14.1 Introduction
14.2 Principle and Theory
 14.3 Gel Electrophoresis
14.4 SDS‐PAGE
14.5 Western Blotting
14.6 Isoelectric Focusing
14.7 Capillary Electrophoresis
15 Mass Spectrometry
15.1 Introduction
15.2 Basic Theory of Mass Spectrometry
15.3 Ionization
15.4 The Mass Spectrometer as a Chromatographic Detector
– Data Acquisition
15.5 Quantitation by MS
15.6 Identification by MS
15.7 Instrumentation
16 Sample Preparation
16.1 When is Sample Preparation Required?
16.2 Main Strategies
16.3 Recovery and Enrichment
16.4 Liquid–Liquid Extraction
16.5 Solid–Liquid Extraction
16.6 Solid Phase Extraction
17 Quality of Analytical Data and Validation
17.1 Instrumental Signals
17.2 Calibration Methods
17.3 Analytical Procedures
17.4 Validation
17.5 System Suitability
18 Chemical Analysis of Pharmaceutical Ingredients
18.1 Pharmaceutical Ingredients, Production, and Control
18.2 Pharmacopoeia Monographs
 18.3 Impurities in Pharmaceutical Ingredients
18.4 Identification of Pharmaceutical Ingredients
18.5 Impurity Testing of Pharmaceutical Ingredients (Pure
Chemical Ingredients)
18.6 Identification and Impurity Testing of Organic Multi‐
Chemical Ingredients
18.7 Assay of Pharmaceutical Ingredients
18.8 Chemical Analysis of Pharmaceutical Ingredients Not
Included in Pharmacopoeias
19 Chemical Analysis of Pharmaceutical Preparations
19.1 Chemical Analysis of Pharmaceutical Preparations
19.2 Monographs and Chemical Analysis
19.3 Identification of the API
19.4 Assay of the Active Pharmaceutical Ingredient
19.5 Chemical Tests for Pharmaceutical Preparations
20 Bioanalysis Chemical Analysis of Pharmaceuticals in
Biological Fluids
20.1 Bioanalysis
20.2 Biological Fluids
20.3 Bioanalytical Methods – An Overview
20.4 Sampling
20.5 Sample Preparation
20.6 Separation and Detection
20.7 Quantitation
20.8 Screening
21 Chemical Analysis of Biopharmaceuticals
21.1 Biopharmaceuticals
21.2 Biopharmaceuticals versus Small Molecule APIs
21.3 Biopharmaceuticals and Pharmacopoeias
21.4 Production of Biopharmaceuticals
 21.5 Identification Procedures for Biopharmaceuticals
(Active Substance)
21.6 Impurity Tests for Biopharmaceuticals (Active
Substances)
21.7 Assay of Biopharmaceuticals (Active Substance)
21.8 Monoclonal Antibodies
21.9 Analysis of Biopharmaceutical Products
21.10 Bioanalysis of Biopharmaceuticals Using LC‐MS/MS
Index
End User License Agreement

List of Tables
Chapter 1
Table 1.1 Excipients in paracetamol tablets and paracetamol
syrup (exam...
Chapter 2
Table 2.1 Requirements for the content of an application for
marketing ...
Table 2.2 Content requirements for application for
marketing authorizat...
Table 2.3 Main elements of the GMP/GLP regulations
Chapter 3
Table 3.1 Common buffers in pharmaceutical analysis
Table 3.2 Log P values for selected active pharmaceutical
ingredients
Chapter 4
Table 4.1 Different types of balances used in pharmaceutical
analysis
Table 4.2 Tolerance for Class 1 and Class 2 balances
(according to Amer...
 Table 4.3 Tolerance of Class A transfer pipettes (according
to American...
Table 4.4 Tolerances for micropipettes (under optimal
conditions)
Table 4.5 Correction factor for the calibration of pipettes
using water...
Table 4.6 Tolerances of Class A volumetric flasks (according
to America...
Table 4.7 Tolerances of Class A burettes (according to
American Society...
Table 4.8 Values of student's t
Table 4.9 Critical values of F at 95% confidence level (two‐
tailed)
Table 4.10 Q critical at 95% confidence level
Chapter 5
Table 5.1 Examples of primary standards in Ph. Eur
Table 5.2 Colour indicators for acid–base titrations
(common examples) ...
Table 5.3 Standard reduction potentials (E0)
Chapter 7
Table 7.1 Solvents for UV spectrophotometry (list is not
complete)
Table 7.2 Absorption maxima for control of wavelength
scale according t...
Table 7.3 Specific absorbance of potassium dichromate
solution for cont...
Chapter 8
Table 8.1 Characteristic infrared absorption bands
Table 8.2 Transmission minima (cm−1) and acceptance
tolerances of...
Chapter 9
Table 9.1 Comparison of methods based on atomic
spectrometry
Chapter 11
Table 11.1 Polarity index and elution strength of selected
solvents in ...
Table 11.2 Ion exchangers
Chapter 12
Table 12.1 Saving of mobile phase as a result of the
reduction in the i...
Table 12.2 LC detectors and their typical performance
Table 12.3 UV cut‐off for common solvents (1 cm path
length)
Chapter 15
Table 15.1 Masses and abundance of stable isotopes
Table 15.2 Typical fragmentations and losses from the
molecular ion (M)...
Chapter 16
Table 16.1 Examples of LLE solvents and their properties
Chapter 17
Table 17.1 General description of an analytical procedure
Chapter 18
Table 18.1 Classification of pharmaceutical ingredients
Table 18.2 Overview of pure chemical ingredients and
multi‐chemical ing...
Table 18.3 Main contents of the Ph.Eur
Table 18.4 Definition of solubility (Ph. Eur.)
Table 18.5 Examples of purity definitions given in Ph. Eur.
and USP for...
 Table 18.6 Overview of common types of impurities in
organic and inorga...
Table 18.7 Overview of the main procedures used for the
identification ...
Table 18.8 Overview of major methods for impurity testing
in Ph. Eur. a...
Table 18.9 Examples of solvents in Classes 1, 2, and 3
according to Ph....
Table 18.10 Classification of element to be considered in the
risk asse...
Table 18.11 Overview of the main techniques for assay of
pharmaceutical...
Chapter 20
Table 20.1 Therapeutic range in plasma of common drugs
subjected to the...
Table 20.2 Protein binding of common drugs
Table 20.3 Efficiency of different approaches to protein
precipitation ...
Chapter 21
Table 21.1 Overview of the amino acids, abbreviations, and
structures
Table 21.2 Overview of the main procedures used for
identification of b...
Table 21.3 Examples of cleavage agents
Table 21.4 Overview of tests revealing related organic
impurities of bi...

List of Illustrations
Chapter 1
 Figure 1.1 Paracetamol (small molecule drug) and insulin
aspart (biopharmac...
Figure 1.2 Illustration of a typical work‐flow for
pharmaceutical manufactu...
Chapter 3
Figure 3.1 Typical basic and acidic functionalities in drug
substances (not...
Figure 3.2 pK a values for selected active pharmaceutical
ingredients
Figure 3.3 Free and protonated form of fluoxetine as
function of pH in aque...
Figure 3.4 Liquid–liquid partition of a drug substance
between water and 1‐...
Figure 3.5 Distribution of ibuprofen (acidic drug substance)
and fluoxetine...
Figure 3.6 Classification of isomers
Figure 3.7 Salicylic acid (2‐hydroxybenzenecarboxylic acid)
and 4‐hydroxybe...
Figure 3.8 Cis–trans isomers of clomiphene
Figure 3.9 Two enantiomers of thalidomide
Figure 3.10 Structure of fluoxetine and fluoxetine
hydrochloride
Figure 3.11 Solubility in water and log D (1‐octanol‐water) of
fluoxetine a...
Figure 3.12 Structure of atenolol
Figure 3.13 Solubility in water and log D (1‐octanol‐water)
of atenolol as ...
Figure 3.14 Structure of morphine
Figure 3.15 Solubility in water and log D (1‐octanol‐water)
of morphine as ...
 Figure 3.16 Structure of ibuprofen
Figure 3.17 Solubility in water and log D (1‐octanol‐water)
of ibuprofen as...
Figure 3.18 Structure of paracetamol
Figure 3.19 Solubility in water and log D (1‐octanol‐water)
of paracetamol ...
Figure 3.20 Structure of hydrocortisone and hydrocortisone
hydrogen succina...
Chapter 4
Figure 4.1 Different steps in a typical procedure in
pharmaceutical analysi...
Figure 4.2 Analytical balance
Figure 4.3 Transfer pipette and measuring pipette
Figure 4.4 Correct position of the meniscus at the
calibration mark
Figure 4.5 Micropipette
Figure 4.6 Volumetric flask
Figure 4.7 Burette
Figure 4.8 Illustration of accuracy and precision
Figure 4.9 Normal distribution of (a) two‐tailed and (b) and
(c) one‐tailed...
Figure 4.10 Confidence limits for a concentration
determined by an unweight...
Figure 4.11 Reading of a burette
Chapter 5
Figure 5.1 Schematic view of the burette used for titration
Figure 5.2 Schematic view of potentiometric titration
Figure 5.3 Titration curve of E versus V and the first
derivative (ΔE/ΔV) v...
 Figure 5.4 Schematic view of the silver–silver chloride
reference electrode
Figure 5.5 Schematic view of the glass combination
electrode with the inter...
Figure 5.6 Titration curve for titration of a strong acid (50
mL of 0.1 M H...
Figure 5.7 Phenolphthalein in acidic and alkaline solution
Figure 5.8 Titration curve for titration of a weak acid (25
mL of 0.1 M sol...
Figure 5.9 Titration curve for titration of weak acids (50 mL
of 0.1 M acid...
Figure 5.10 Titration curve for titration of 50 mL of 0.1 M
sodium carbonat...
Figure 5.11 Redox titration of 50 mL 0.1 M Fe2+ with 0.1 M
Ce4+
Figure 5.12 Redox titration curves with different reaction
potentials
Figure 5.13 Complexation reaction of calcium with EDTA
Chapter 6
Figure 6.1 Representation of a beam of monochromatic
radiation
Figure 6.2 The electromagnetic spectrum
Figure 6.3 Colours of visible light. When the compound
absorbs light of a w...
Figure 6.4 UV spectra of acetylsalicylic acid and
paracetamol
Figure 6.5 UV‐Vis spectrum of the orange coloured
substance riboflavin
Figure 6.6 Absorption and fluorescence spectra of quinine
Figure 6.7 Absorption spectrum of sodium in the gas phase
Chapter 7
Figure 7.1 Beer's law – absorption of radiation
Figure 7.2 Absorption spectrum
Figure 7.3 Absorption spectra of 1,2,4‐triazine in vapour,
hexane, and wate...
Figure 7.4 Absorption of radiation is dependent on pH. The
UV spectra of ph...
Figure 7.5 UV spectrum for paracetamol
Figure 7.6 Schematic view of a UV spectrophotometer
Figure 7.7 Schematic view of a monochromator based on a
reflection grating
Figure 7.8 A simplified diode array configuration
Figure 7.9 Schematic view of a double‐beam
spectrophotometer
Figure 7.10 Calibration curves at different wavelengths
Figure 7.11 Holmium perchlorate absorption spectrum
Figure 7.12 Schematic view of a fluorimeter
Chapter 8
Figure 8.1 Basic principle of IR spectrophotometry
Figure 8.2 IR and UV spectra of salicylic acid
Figure 8.3 IR spectrum of water (bottom) and carbon
dioxide (top)
Figure 8.4 Recording by transmission
Figure 8.5 Recording by diffuse reflectance
Figure 8.6 Recording by attenuated total reflectance (ATR)
Chapter 9
Figure 9.1 Principle of flame atomic absorption
spectrometry
Figure 9.2 Schematic view of the hollow cathode lamp
 Figure 9.3 Schematic view of the atomization device
Figure 9.4 Schematic view of the electrothermal atomizer
Figure 9.5 Principle of atomic emission spectrometry
Figure 9.6 Schematic view of the inductively coupled
plasma torch
Figure 9.7 Schematic view of the ICP‐MS instrument
Chapter 10
Figure 10.1 Chromatographic separation of components A,
B, and C
Figure 10.2 Schematic view of the chromatographic system
Figure 10.3 Chromatogram of a sample containing
compounds A, B, and C
Figure 10.4 Retention time, retention volume, hold‐up time,
and hold‐up vol...
Figure 10.5 Chromatogram illustrating retention time and
retention factor
Figure 10.6 Parameters used to measure peak width
Figure 10.7 Retention factors of two closely eluting peaks
Figure 10.8 Parameters needed for calculation of

Figure 10.9 Effect of inadequate retention, low separation

factor, and poor...
Figure 10.10 Parameters used to calculate peak symmetry
and illustration of...
Figure 10.11 Chromatographic bands (peaks) are broadened
during the transpo...
Figure 10.12 van Deemter curve illustating separation
efficiency (H) as a f...
Figure 10.13 Irregular particles of the column material
result in different...
 Figure 10.14 Longitudinal diffusion – sample molecules
diffuse from high co...
Chapter 11
Figure 11.1 Separation of acetaminophen, pseudoephedrine,
doxylamine, and d...
Figure 11.2 Silica gel – the basis of stationary phase
particles
Figure 11.3 Chemical reaction of silica with different
chlorosilane reagent...
Figure 11.4 Hydrophobic interactions between C18
(stationary phase) and nap...
Figure 11.5 Separation in order of increasing hydrophobicity
by RP chromato...
Figure 11.6 Reversed‐phase chromatography with the C18
and the C8 stationar...
Figure 11.7 Effect of percentage of acetonitrile in the mobile
phase
Figure 11.8 Mobile phases with similar eluting strengths
Figure 11.9 Illustration of solvent selectivity in RP
chromatography
Figure 11.10 Viscosity of mixtures of water and organic
solvents
Figure 11.11 Separation of acidic drugs (fenoprofen and
ibuprofen) and basi...
Figure 11.12 Structures of (sodium) octanesulfonate,
heptafluorobutyrate (h...
Figure 11.13 Comparison of RP chromatography and ion‐
pair chromatography. T...
Figure 11.14 Silanol groups on the surface of silica
Figure 11.15 NP chromatography of vitamin E variants. The
stationary phase ...
 Figure 11.16 Contribution of different functional groups to
interaction and...
Figure 11.17 TLC procedure: the sample is applied to the
TLC plate, separat...
Figure 11.18 Parameters for determination of R f values
Figure 11.19 Examples of HILIC stationary phases
Figure 11.20 Principle of hydrophilic interaction liquid
chromatography (HI...
Figure 11.21 Separation of amino acids by hydrophilic
interaction liquid ch...
Figure 11.22 Ion exchange chromatography separation of
small anions. The st...
Figure 11.23 Principle of size exclusion chromatography
Figure 11.24 SEC separation of thyroglobulin (660 kDa),
IgG (150 kDa), BSA ...
Figure 11.25 Separation of L‐ and D‐epinephrine using a
chiral stationary p...
Figure 11.26 Phase diagram for carbon dioxide
Chapter 12
Figure 12.1 Schematic view of LC system
Figure 12.2 Height equivalent to a theoretical plate as a
function of the f...
Figure 12.3 LC separation using columns of different
packing material size
Figure 12.4 Schematic view of a piston pump
Figure 12.5 Isocratic and gradient elution of a sample
containing analytes ...
Figure 12.6 Schematic view of a loop injector
Figure 12.7 Schematic view of a UV detector
Figure 12.8 Schematic view of the flow cell in a UV detector
 Figure 12.9 Schematic view of a diode array detector (DAD)
Figure 12.10 Schematic view of a fluorescence detector
Figure 12.11 Excitation and emission spectra of quinine
Chapter 13
Figure 13.1 Schematic illustration of a gas chromatograph
Figure 13.2 GC analysis of peppermint essential oil
Figure 13.3 Isothermal versus temperature programming in
GC analysis of n‐a...
Figure 13.4 van Deemter plots with different carrier gases
Figure 13.5 Basic skeletons of polydimethylsiloxane,
polyphenylmethylsiloxa...
Figure 13.6 Basic skeleton of polyethylene glycol
Figure 13.7 Capillary column (wall‐coated) for GC
Figure 13.8 Split/splitless injector for capillary GC
Figure 13.9 Static headspace injection of residual solvent
Figure 13.10 Schematic view of a flame ionization detector
(FID)
Figure 13.11 Schematic view of an electron capture detector
Figure 13.12 Silylation of a hydroxyl group
Figure 13.13 Methylation of fatty acids in oils
Figure 13.14 Derivatization of α‐amino acid with
trifluoroacetic acid anhyd...
Chapter 14
Figure 14.1 Charged compounds in solution migrate under
application of an e...
Figure 14.2 Schematic view of zone electrophoresis in a
capillary
Figure 14.3 Principle of gel electrophoresis
 Figure 14.4 Slab gel electrophoresis of DNA fragments
containing 100, 250, ...
Figure 14.5 Setup for slab‐gel electrophoresis with samples
and standard
Figure 14.6 Principle of sodium dodecyl sulfate
polyacrylamide gel electrop...
Figure 14.7 SDS‐PAGE separation of proteins of 20, 30, 43,
67, and 93 kDa
Figure 14.8 Principle of Western blotting
Figure 14.9 Principle of isoelectric focusing
Figure 14.10 Schematic overview of capillary electrophoresis
Figure 14.11 Inner surface of capillary with electrical double
layer and el...
Figure 14.12 Flow profiles in CE (electro‐osmotic flow) and
LC (pressure dr...
Figure 14.13 Stacking of cations at low pH
Figure 14.14 Hydrodynamic injection
Chapter 15
Figure 15.1 Schematic views of LC‐MS and GC‐MS
Figure 15.2 Mass spectrum of chlorambucil in the m/z
range 250–310 by elect...
Figure 15.3 GC‐MS total ion current chromatogram and
extracted ion chromato...
Figure 15.4 Areas of co‐eluting peaks can be separated as
the analytes have...
Figure 15.5 Isotope patterns of chlorine (one and two atoms
35Cl and 37Cl) ...

Figure 15.6 Electrospray mass spectrum of the insulin

monomer (C257H383N65O
 Figure 15.7 Unit resolution and high resolution spectra of
the peak at m/z ...
Figure 15.8 Schematic view of mass spectrometer
Figure 15.9 Schematic view of electrospray ionization
Figure 15.10 Schematic view of atmospheric pressure
chemical ionization
Figure 15.11 Schematic view of quadrupole mass analyser
Figure 15.12 Schematic view of triple quadrupole mass
analyser
Figure 15.13 Comparison of full scan (extracted ion
chromatogram), SIM, and...
Figure 15.14 Schematic view of ion trap mass analyser
Figure 15.15 Schematic view of time‐of‐flight mass
spectrometry
Chapter 16
Figure 16.1 Principle of LLE
Figure 16.2 Distribution ratio (as log D) as a function of pH
for an acidic...
Figure 16.3 Distribution ratio (as log D) as a function of pH
for a basic a...
Figure 16.4 Principle of SLE
Figure 16.5 Principle of SPE
Figure 16.6 SPE column
Figure 16.7 Conditioning and solvation of a reversed‐phase
SPE column
Figure 16.8 SPE vacuum manifold.
Figure 16.9 Different sorbents for reversed‐phase SPE
Figure 16.10 Example of polymeric sorbent for SPE
Figure 16.11 Secondary interactions in SPE
 Figure 16.12 Examples of sorbents for ion exchange SPE
Figure 16.13 Retention of amphetamine on a strong cation
exchange SPE colum...
Figure 16.14 Retention of amphetamine on a mixed‐mode
SPE column
Figure 16.15 Polymeric‐based sorbent for mixed‐mode SPE
Figure 16.16 Examples of sorbents for normal‐phase SPE
Chapter 17
Figure 17.1 Peak height and peak area of a chromatographic
peak
Figure 17.2 Chromatogram of analyte and internal standard
Figure 17.3 Atovaquone (analyte) and atovaquone‐D5
(internal standard)
Figure 17.4 Analytical characteristics used in validation of
an analytical ...
Figure 17.5 Characteristics applicable to analytical
procedures
Figure 17.6 Definition of S and N. S/N is close to 3 is this
illustration
Figure 17.7 Relationship between concentration and
precision (relative stan...
Figure 17.8 Illustration of linearity
Chapter 18
Figure 18.1 Synthesis scheme for ibuprofen (top frame) and
possible by‐prod...
Figure 18.2 The general chemical structure of polyethylene
glycol, with mol...
Figure 18.3 Description of method of analysis for the
melting point (Ph. Eu...
 Figure 18.4 Descriptions of anhydrous acetic acid, lead
standard solution, ...
Figure 18.5 Ph. Eur. monograph for paracetamol.
Figure 18.6 USP monograph for acetaminophen
(paracetamol).
Figure 18.7 Ph. Eur. monograph for Castor oil, virgin.
Figure 18.8 First and second identification for mianserin
hydrochloride (Ph...
Figure 18.9 Schematic view of an apparatus for melting
point determination
Figure 18.10 Visualization of the chirality concept
Figure 18.11 Principle for measurement of optical rotation
Figure 18.12 Infrared absorption spectra of morphine base
(top), morphine h...
Figure 18.13 Appearance of solution
Figure 18.14 Related substances for omeprazole
Figure 18.15 Potential sources of elemental impurities
Chapter 20
Figure 20.1 Schematic view of the drug development
process
Figure 20.2 The composition of blood
Figure 20.3 The steps of a bioanalytical method
Figure 20.4 Principle of protein precipitation
Chapter 21
Figure 21.1 Overview of the four levels of protein structure.
Introduction to
Pharmaceutical Analytical
Chemistry

STIG PEDERSEN-BJERGAARD
Department of Pharmacy, University of Oslo, Norway and
Department of Pharmacy, University of Copenhagen, Denmark

BENTE GAMMELGAARD
Department of Pharmacy, University of Copenhagen, Denmark

TRINE GRØNHAUG HALVORSEN

Department of Pharmacy, University of Oslo, Norway

Second Edition
Copyright
This edition first published 2019
© 2019 John Wiley & Sons Ltd

Edition history:
“John Wiley & Sons Ltd. (1e, 2012)”.

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Library of Congress Cataloging‐in‐Publication Data

Names: Pedersen-Bjergaard, Stig, author. | Gammelgaard, Bente, author. |

Halvorsen, Trine G. (Trine Grønhaug), 1975- author.
Title: Introduction to pharmaceutical analytical chemistry / Stig
Pedersen-Bjergaard, Department of Pharmacy, University of Oslo, Norway and
Department of Pharmacy, University of Copenhagen, Denmark, Bente
Gammelgaard, Department of Pharmacy, University of Copenhagen,
Denmark,Trine Grønhaug Halvorsen, Department of Pharmacy, University of
Oslo,
Norway.
Other titles: Introduction to pharmaceutical chemical analysis.
Description: Second edition. | Hoboken, NJ : Wiley, 2019. | Revision of:
Introduction to pharmaceutical chemical analysis / Steen Hansen, Stig
Pedersen-Bjergaard, Knut Rasmussen. 2012. | Includes bibliographical
references and index. |
Identifiers: LCCN 2018051420 (print) | LCCN 2018053744 (ebook) | ISBN
9781119362722 (Adobe PDF) | ISBN 9781119362753 (ePub) | ISBN 9781119362722
(paperback)
Subjects: LCSH: Drugs–Analysis. | Pharmaceutical chemistry. | BISAC: SCIENCE
/ Chemistry / Analytic.
Classification: LCC RS189 (ebook) | LCC RS189 .H277 2019 (print) | DDC
615.1/9–dc23
LC record available at https://lccn.loc.gov/2018051420

Cover design: Wiley

Preface to the Second Edition
This textbook is an extensive revision of ‘Introduction to
Pharmaceutical Analysis’ from 2012. We have revised the
manuscript totally, and updated the content according to current
practice in pharmaceutical analytical chemistry, and according to
current versions of European and United States Pharmacopeia.
Additionally, we have added a new chapter on chemical analysis of
biopharmaceuticals, improved the illustrations throughout and
provided illustrations in colour. The intention of these efforts has
been to provide the reader with a textbook at the level expected in
2018.
We have changed the title to emphasize that this textbook is about
analytical chemistry, and that the applications described are all
related to pharmaceuticals. However, the philosophy is the same as
with the first edition. The textbook is primarily for pharmacy and
chemistry students (and other scientists approaching the
pharmaceutical sciences) at university level, requesting basic
knowledge on chemical analysis of pharmaceutical ingredients and
preparations, and chemical analysis of drug substances in biological
fluids. In the first part of the textbook, we teach the fundamentals of
the main analytical techniques. Compared to textbooks in pure
analytical chemistry, we go into less detail but we still teach to a level
where the reader can understand the details in current
pharmacopeia and bioanalytical methods. The second part of the
textbook is unique, as we focus on identification, purity testing and
assay of pharmaceutical ingredients, identification and quantitation
of active ingredients in pharmaceutical preparations, and
identification and quantitation of drugs in biological fluids. Such
systematic discussion of pharmaceutical applications is not found in
any other textbook on the market.
Originally, this textbook was written in Norwegian by Stig Pedersen‐
Bjergaard and Knut Rasmussen. The first Norwegian edition came in
2004 (ISBN 82‐7674‐844‐9), and this was revised in 2010 (ISBN
978‐82‐450‐1013‐8). The manuscript was translated to English and
improved by Stig Pedersen‐Bjergaard, Knut Rasmussen, and Steen
Honoré Hansen in 2012. Since that first English edition, the author
team has changed. Knut Rasmussen has retired and Steen Honoré
Hansen passed away in the autumn 2017. Knut is acknowledged for
his pioneering work in the period 2004–2012, and for his highly
valuable advice during preparation of the current edition. Steen is
acknowledged for his work on translation and improvements in
preparation of the first English edition of the book, and the valuable
discussions of the content and improvements of the present edition
until autumn 2017. We also thank our colleagues and students at the
University of Oslo and the University of Copenhagen for inspiration,
discussions, advice, proof reading, chromatograms, titration curves,
and fun.

Oslo/Copenhagen, June 2018

Stig Pedersen‐Bjergaard Bente Gammelgaard Trine Grønhaug
Halvorsen
University of Oslo University of Copenhagen University of Oslo
University of Copenhagen
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