The definitive textbook on the chemical analysis of pharmaceutical drugs – fully revised and updated
Introduction to Pharmaceutical Analytical Chemistry enables students to gain fundamental knowledge of the vital concepts, techniques and applications of the chemical analysis of pharmaceutical ingredients, final pharmaceutical products and drug substances in biological fluids. A unique emphasis on pharmaceutical laboratory practices, such as sample preparation and separation techniques, provides an efficient and practical educational framework for undergraduate studies in areas such as pharmaceutical sciences, analytical chemistry and forensic analysis. Suitable for foundational courses, this essential undergraduate text introduces the common analytical methods used in quantitative and qualitative chemical analysis of pharmaceuticals.
This extensively revised second edition includes a new chapter on chemical analysis of biopharmaceuticals, which includes discussions on identification, purity testing and assay of peptide and protein-based formulations. Also new to this edition are improved colour illustrations and tables, a streamlined chapter structure and text revised for increased clarity and comprehension.
Introduces the fundamental concepts of pharmaceutical analytical chemistry and statistics Presents a systematic investigation of pharmaceutical applications absent from other textbooks on the subject Examines various analytical techniques commonly used in pharmaceutical laboratories Provides practice problems, up-to-date practical examples and detailed illustrations Includes updated content aligned with the current European and United States Pharmacopeia regulations and guidelines
Covering the analytical techniques and concepts necessary for pharmaceutical analytical chemistry, Introduction to Pharmaceutical Analytical Chemistry is ideally suited for students of chemical and pharmaceutical sciences as well as analytical chemists transitioning into the field of pharmaceutical analytical chemistry.
Preface to the Second Edition xv Abbreviations xvii Symbols and Units xxi 1 Introduction to Pharmaceutical Analytical Chemistry 1 1.1 Introduction 1 1.2 Pharmaceutical Analytical Chemistry 4 1.3 This Textbook 7 2 Marketing Authorizations, Pharmaceutical Manufacturing, and International Pharmacopoeias 9 2.1 Introduction 9 2.2 Marketing Authorization and Industrial Production 10 2.3 Pharmacopoeias 13 2.4 Life Time of Pharmaceutical Preparations and Ingredients 14 3 Fundamentals of Bases, Acids, Solubility, Polarity, Partition, and Stereochemistry 17 3.1 Acids, Bases, pH, and pKa 17 3.2 Buffers 19 3.3 Acid and Base Properties of Drug Substances 20 3.4 Distribution Between Phases 21 3.5 Stereoisomers 26 3.6 Active Pharmaceutical Ingredients – A Few Examples 28 3.7 Stability of Drug Substances 34 4 Fundamentals of Pharmaceutical Analytical Chemistry 37 4.1 Pharmaceutical Analytical Chemistry 37 4.2 How to Specify Quantities, Concentrations, and Compositions of Mixtures 39 4.3 Laboratory Equipment 43 4.4 How to Make Solutions and Dilutions 52 4.5 Errors, Accuracy, and Precision 54 4.6 Statistical Tests 56 4.7 Linear Regression Analysis 65 4.8 How to Present an Analytical Result 68 4.9 Additional Words and Terms 70 5 Titration 73 5.1 Introduction 73 5.2 Potentiometric Titration and Electrodes 79 5.3 Aqueous Acid–Base Titrations 82 5.4 Titration in Non-aqueous Solvents 88 5.5 Redox Titrations 91 5.6 Alternative Principles of Titration 95 6 Introduction to Spectroscopic Methods 97 6.1 Electromagnetic Radiation 97 6.2 Molecules and Absorption of Electromagnetic Radiation 99 6.3 Absorbing Structures – Chromophores 101 6.4 Fluorescence 101 6.5 Atoms and Electromagnetic Radiation 102 7 UV-Vis Spectrophotometry 105 7.1 Areas of Use 105 7.2 Quantitation 106 7.3 Absorbance Dependence on Measurement Conditions 108 7.4 Identification 110 7.5 Instrumentation 111 7.6 Practical Work and Method Development 115 7.7 Test of Spectrophotometers 116 7.8 Fluorimetry 119 8 IR Spectrophotometry 121 8.1 IR Spectrophotometry 121 8.2 Instrumentation 125 8.3 Recording by Transmission, Diffuse Reflectance, and Attenuated Total Reflection 125 8.4 Instrument Calibration 128 8.5 NIR Spectrophotometry 129 9 Atomic Spectrometry 131 9.1 Applications of Atomic Spectrometry 131 9.2 Atomic Absorption Spectrometry (AAS) 132 9.3 AAS Instrumentation 132 9.4 AAS Practical Work and Method Development 137 9.5 Atomic Emission Spectrometry (AES) 138 9.6 Flame Photometry 139 9.7 Inductively Coupled Plasma Emission Spectrometry 140 9.8 Inductively Coupled Plasma Mass Spectrometry 141 10 Introduction to Chromatography 143 10.1 Introduction 143 10.2 General Principles 144 10.3 Retention 146 10.4 Efficiency 149 10.5 Selectivity 151 10.6 Resolution 152 10.7 Peak Symmetry 154 10.8 The Dynamics of Chromatography 155 11 Separation Principles in Liquid Chromatography 159 11.1 Introduction 159 11.2 Reversed-Phase Chromatography 160 11.3 Ion-Pair Chromatography 168 11.4 Normal-Phase Chromatography 170 11.5 Thin-Layer Chromatography 173 11.6 Hydrophilic Interaction Chromatography 175 11.7 Ion Exchange Chromatography 177 11.8 Size Exclusion Chromatography 178 11.9 Chiral Separations 180 11.10 Supercritical Fluid Chromatography 182 12 High Performance Liquid Chromatography 185 12.1 Introduction 185 12.2 The Column 186 12.3 Scaling Between Columns 188 12.4 Pumps 189 12.5 Injectors 191 12.6 Detectors 192 12.7 Mobile Phases 197 12.8 Solvents for Sample Preparation 198 13 Gas Chromatography 199 13.1 Introduction 199 13.2 Basic Principle 200 13.3 Instrumentation 201 13.4 Carrier Gas 203 13.5 Stationary Phases 205 13.6 Retention 207 13.7 Columns 208 13.8 Injection 209 13.9 Detectors 211 13.10 Derivatization 213 14 Electrophoretic Methods 215 14.1 Introduction 215 14.2 Principle and Theory 216 14.3 Gel Electrophoresis 218 14.4 SDS-PAGE 220 14.5 Western Blotting 221 14.6 Isoelectric Focusing 223 14.7 Capillary Electrophoresis 223 15 Mass Spectrometry 231 15.1 Introduction 231 15.2 Basic Theory of Mass Spectrometry 233 15.3 Ionization 235 15.4 The Mass Spectrometer as a Chromatographic Detector – Data Acquisition 236 15.5 Quantitation by MS 238 15.6 Identification by MS 238 15.7 Instrumentation 251 16 Sample Preparation 259 16.1 When is Sample Preparation Required? 259 16.2 Main Strategies 260 16.3 Recovery and Enrichment 261 16.4 Liquid–Liquid Extraction 263 16.5 Solid–Liquid Extraction 269 16.6 Solid Phase Extraction 270 17 Quality of Analytical Data and Validation 281 17.1 Instrumental Signals 281 17.2 Calibration Methods 282 17.3 Analytical Procedures 290 17.4 Validation 291 17.5 System Suitability 301 18 Chemical Analysis of Pharmaceutical Ingredients 305 18.1 Pharmaceutical Ingredients, Production, and Control 306 18.2 Pharmacopoeia Monographs 308 18.3 Impurities in Pharmaceutical Ingredients 321 18.4 Identification of Pharmaceutical Ingredients 324 18.5 Impurity Testing of Pharmaceutical Ingredients (Pure Chemical Ingredients) 344 18.6 Identification and Impurity Testing of Organic Multi-Chemical Ingredients 368 18.7 Assay of Pharmaceutical Ingredients 375 18.8 Chemical Analysis of Pharmaceutical Ingredients Not Included in Pharmacopoeias 388 19 Chemical Analysis of Pharmaceutical Preparations 389 19.1 Chemical Analysis of Pharmaceutical Preparations 389 19.2 Monographs and Chemical Analysis 390 19.3 Identification of the API 395 19.4 Assay of the Active Pharmaceutical Ingredient 410 19.5 Chemical Tests for Pharmaceutical Preparations 427 20 Bioanalysis Chemical Analysis of Pharmaceuticals in Biological Fluids 433 20.1 Bioanalysis 433 20.2 Biological Fluids 438 20.3 Bioanalytical Methods – An Overview 440 20.4 Sampling 440 20.5 Sample Preparation 441 20.6 Separation and Detection 446 20.7 Quantitation 447 20.8 Screening 453 21 Chemical Analysis of Biopharmaceuticals 459 21.1 Biopharmaceuticals 459 21.2 Biopharmaceuticals versus Small Molecule APIs 463 21.3 Biopharmaceuticals and Pharmacopoeias 464 21.4 Production of Biopharmaceuticals 465 21.5 Identification Procedures for Biopharmaceuticals (Active Substance) 467 21.6 Impurity Tests for Biopharmaceuticals (Active Substances) 488 21.7 Assay of Biopharmaceuticals (Active Substance) 498 21.8 Monoclonal Antibodies 500 21.9 Analysis of Biopharmaceutical Products 502 21.10 Bioanalysis of Biopharmaceuticals Using LC-MS/MS 503 Index 505
STIG PEDERSEN-BJERGAARD is Professor at the Department of Pharmacy, University of Oslo and Professor at the Department of Pharmacy, University of Copenhagen. BENTE GAMMELGAARD is Professor at the Department of Pharmacy, University of Copenhagen. TRINE GRØNHAUG HALVORSEN is Associate Professor at the Department of Pharmacy, University of Oslo.
