Introduction to Pharmaceutical Analytical Chemistry

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.

• Preface to the Second Edition xvAbbreviations xviiSymbols and Units xxi1 Introduction to Pharmaceutical Analytical Chemistry 11.1 Introduction 11.2 Pharmaceutical Analytical Chemistry 41.3 This Textbook 72 Marketing Authorizations, Pharmaceutical Manufacturing, and International Pharmacopoeias 92.1 Introduction 92.2 Marketing Authorization and Industrial Production 102.3 Pharmacopoeias 132.4 Life Time of Pharmaceutical Preparations and Ingredients 143 Fundamentals of Bases, Acids, Solubility, Polarity, Partition, and Stereochemistry 173.1 Acids, Bases, pH, and pKa 173.2 Buffers 193.3 Acid and Base Properties of Drug Substances 203.4 Distribution Between Phases 213.5 Stereoisomers 263.6 Active Pharmaceutical Ingredients – A Few Examples 283.7 Stability of Drug Substances 344 Fundamentals of Pharmaceutical Analytical Chemistry 374.1 Pharmaceutical Analytical Chemistry 374.2 How to Specify Quantities, Concentrations, and Compositions of Mixtures 394.3 Laboratory Equipment 434.4 How to Make Solutions and Dilutions 524.5 Errors, Accuracy, and Precision 544.6 Statistical Tests 564.7 Linear Regression Analysis 654.8 How to Present an Analytical Result 684.9 Additional Words and Terms 705 Titration 735.1 Introduction 735.2 Potentiometric Titration and Electrodes 795.3 Aqueous Acid–Base Titrations 825.4 Titration in Non-aqueous Solvents 885.5 Redox Titrations 915.6 Alternative Principles of Titration 956 Introduction to Spectroscopic Methods 976.1 Electromagnetic Radiation 976.2 Molecules and Absorption of Electromagnetic Radiation 996.3 Absorbing Structures – Chromophores 1016.4 Fluorescence 1016.5 Atoms and Electromagnetic Radiation 1027 UV-Vis Spectrophotometry 1057.1 Areas of Use 1057.2 Quantitation 1067.3 Absorbance Dependence on Measurement Conditions 1087.4 Identification 1107.5 Instrumentation 1117.6 Practical Work and Method Development 1157.7 Test of Spectrophotometers 1167.8 Fluorimetry 1198 IR Spectrophotometry 1218.1 IR Spectrophotometry 1218.2 Instrumentation 1258.3 Recording by Transmission, Diffuse Reflectance, and Attenuated Total Reflection 1258.4 Instrument Calibration 1288.5 NIR Spectrophotometry 1299 Atomic Spectrometry 1319.1 Applications of Atomic Spectrometry 1319.2 Atomic Absorption Spectrometry (AAS) 1329.3 AAS Instrumentation 1329.4 AAS Practical Work and Method Development 1379.5 Atomic Emission Spectrometry (AES) 1389.6 Flame Photometry 1399.7 Inductively Coupled Plasma Emission Spectrometry 1409.8 Inductively Coupled Plasma Mass Spectrometry 14110 Introduction to Chromatography 14310.1 Introduction 14310.2 General Principles 14410.3 Retention 14610.4 Efficiency 14910.5 Selectivity 15110.6 Resolution 15210.7 Peak Symmetry 15410.8 The Dynamics of Chromatography 15511 Separation Principles in Liquid Chromatography 15911.1 Introduction 15911.2 Reversed-Phase Chromatography 16011.3 Ion-Pair Chromatography 16811.4 Normal-Phase Chromatography 17011.5 Thin-Layer Chromatography 17311.6 Hydrophilic Interaction Chromatography 17511.7 Ion Exchange Chromatography 17711.8 Size Exclusion Chromatography 17811.9 Chiral Separations 18011.10 Supercritical Fluid Chromatography 18212 High Performance Liquid Chromatography 18512.1 Introduction 18512.2 The Column 18612.3 Scaling Between Columns 18812.4 Pumps 18912.5 Injectors 19112.6 Detectors 19212.7 Mobile Phases 19712.8 Solvents for Sample Preparation 19813 Gas Chromatography 19913.1 Introduction 19913.2 Basic Principle 20013.3 Instrumentation 20113.4 Carrier Gas 20313.5 Stationary Phases 20513.6 Retention 20713.7 Columns 20813.8 Injection 20913.9 Detectors 21113.10 Derivatization 21314 Electrophoretic Methods 21514.1 Introduction 21514.2 Principle and Theory 21614.3 Gel Electrophoresis 21814.4 SDS-PAGE 22014.5 Western Blotting 22114.6 Isoelectric Focusing 22314.7 Capillary Electrophoresis 22315 Mass Spectrometry 23115.1 Introduction 23115.2 Basic Theory of Mass Spectrometry 23315.3 Ionization 23515.4 The Mass Spectrometer as a Chromatographic Detector – Data Acquisition 23615.5 Quantitation by MS 23815.6 Identification by MS 23815.7 Instrumentation 25116 Sample Preparation 25916.1 When is Sample Preparation Required? 25916.2 Main Strategies 26016.3 Recovery and Enrichment 26116.4 Liquid–Liquid Extraction 26316.5 Solid–Liquid Extraction 26916.6 Solid Phase Extraction 27017 Quality of Analytical Data and Validation 28117.1 Instrumental Signals 28117.2 Calibration Methods 28217.3 Analytical Procedures 29017.4 Validation 29117.5 System Suitability 30118 Chemical Analysis of Pharmaceutical Ingredients 30518.1 Pharmaceutical Ingredients, Production, and Control 30618.2 Pharmacopoeia Monographs 30818.3 Impurities in Pharmaceutical Ingredients 32118.4 Identification of Pharmaceutical Ingredients 32418.5 Impurity Testing of Pharmaceutical Ingredients (Pure Chemical Ingredients) 34418.6 Identification and Impurity Testing of Organic Multi-Chemical Ingredients 36818.7 Assay of Pharmaceutical Ingredients 37518.8 Chemical Analysis of Pharmaceutical Ingredients Not Included in Pharmacopoeias 38819 Chemical Analysis of Pharmaceutical Preparations 38919.1 Chemical Analysis of Pharmaceutical Preparations 38919.2 Monographs and Chemical Analysis 39019.3 Identification of the API 39519.4 Assay of the Active Pharmaceutical Ingredient 41019.5 Chemical Tests for Pharmaceutical Preparations 42720 Bioanalysis Chemical Analysis of Pharmaceuticals in Biological Fluids 43320.1 Bioanalysis 43320.2 Biological Fluids 43820.3 Bioanalytical Methods – An Overview 44020.4 Sampling 44020.5 Sample Preparation 44120.6 Separation and Detection 44620.7 Quantitation 44720.8 Screening 45321 Chemical Analysis of Biopharmaceuticals 45921.1 Biopharmaceuticals 45921.2 Biopharmaceuticals versus Small Molecule APIs 46321.3 Biopharmaceuticals and Pharmacopoeias 46421.4 Production of Biopharmaceuticals 46521.5 Identification Procedures for Biopharmaceuticals (Active Substance) 46721.6 Impurity Tests for Biopharmaceuticals (Active Substances) 48821.7 Assay of Biopharmaceuticals (Active Substance) 49821.8 Monoclonal Antibodies 50021.9 Analysis of Biopharmaceutical Products 50221.10 Bioanalysis of Biopharmaceuticals Using LC-MS/MS 503Index 505