Introduction to Pharmaceutical Chemical Analysis

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Format: Hardcover
Pub. Date: 2011-12-12
Publisher(s): Wiley
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Summary

This textbook is the first to present a systematic introduction to chemical analysis of pharmaceutical raw materials, finished pharmaceutical products, and of drugs in biological fluids, which are carried out in pharmaceutical laboratories worldwide. In addition, this textbook teaches the fundamentals of all the major analytical techniques used in the pharmaceutical laboratory, and teaches the international pharmacopoeias and guidelines of importance for the field. It is primarily intended for the pharmacy student, to teach the requirements in "analytical chemistry" for the 5 years pharmacy curriculum, but the textbook is also intended for analytical chemists moving into the field of pharmaceutical analysis. Addresses the basic concepts, then establishes the foundations for the common analytical methods that are currently used in the quantitative and qualitative chemical analysis of pharmaceutical drugs Provides an understanding of common analytical techniques used in all areas of pharmaceutical development Suitable for a foundation course in chemical and pharmaceutical sciences Aimed at undergraduate students of degrees in Pharmaceutical Science/Chemistry Analytical Science/Chemistry, Forensic analysis Includes many illustrative examples

Author Biography

Steen Hansen is professor in analytical chemistry at the Faculty of Pharmaceutical Sciences at Copenhagen University (Denmark), and has extensive experience in the teaching of analytical chemistry for pharmacy students. His main research interests are in basic separation sciences (primarily HPLC and CE), in particular on separation mechanisms, but also extend into hyphenated techniques using NMR and ICP-MS besides conventional detection techniques. He has authored and/or coauthored more than 240 papers in international peer-review journals. For 20 years, he was the President of the Scandinavian Section of The Chromatographic Discussion Group until this was renamed the Separation Sciences Foundation of which he is President.

Knut Einar Rasmussen is professor in pharmacy at the School of Pharmacy at University of Oslo (Norway) and has similarly long experience in teaching of drug analysis for Pharmacy students. He has published extensively and his main research areas are focused on the development of innovative state-of-the-art miniaturized methods in separation science combined with detection and structure determination of drugs, naturally occurring biomolecules/biomarkers and environmental biomarkers.

Stig Pedersen-Bjergaard is professor at at the School of Pharmacy, University of Oslo (Oslo, Norway) as well as in 2008, being appointed as full Professor (part time) at Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen (Copenhagen, Denmark). SPB has specialized in analytical micro extraction technologies, on development and applications of artificial liquid membranes, and on electrokinetic separation methods. SPB has published more than 90 papers in international journals, given more than 65 presentations at international symposia, authored 6 patent applications, and is a member of the Editorial board for Analytica Chimica Acta and International Journal of Analytical Chemistry.

Table of Contents

Prefacep. xv
Introduction to Pharmaceutical Analysisp. 1
Applications and Definitionsp. 1
The Life of Medicinesp. 4
The Quality of Medical Productsp. 8
Summaryp. 11
International Pharmacopoeias, Regulations and Guidelinesp. 13
Overview of Legislationp. 13
Legislation and Regulations for Industrial Productionp. 14
Life Time of Drugs and Drug Substancesp. 17
Pharmacopoeiasp. 18
International Harmonizationp. 19
International Conference on Harmonizationp. 20
Pharmacopoeial Discussion Groupp. 20
Legislation and Regulations for Pharmacy Productionp. 20
Summaryp. 21
Fundamental Chemical Properties, Buffers and pHp. 23
pH and pKap. 23
Partitionp. 25
Stereochemistryp. 28
Stability Testingp. 29
Summaryp. 30
Fundamentals of Pharmaceutical Analysisp. 33
What is a Pharmaceutical (Chemical) Analysis?p. 33
How to Specify Quantities and Concentrations?p. 35
Basic Laboratory Equipmentp. 37
The Analytical Balancep. 37
Pipettesp. 41
Volumetric Flasksp. 44
Burettesp. 47
How to Make Solutions and Dilutionsp. 47
Calibration of Analytical Methodsp. 49
Errors, Accuracy, and Precisionp. 50
Systematic and Random Errorsp. 50
Accuracy and Precisionp. 51
Statisticsp. 52
Mean Value and Standard Deviationp. 52
Confidence Intervalsp. 54
Comparison of Means with a t-Testp. 55
Q-Test to Reject Outliersp. 56
Linear Regression with the Method of Least Squaresp. 57
How to Present an Analytical Resultp. 58
Some Words and Conceptsp. 62
Analysis and Determinationp. 62
Sample Replicates and Measuring Replicatesp. 62
Interferencep. 62
Blind Samplesp. 62
Titrimetric Methodsp. 65
Introductionp. 65
Acid-Base Titrationsp. 72
Acid-Base Titrations in Non-Aqueous Mediap. 75
Redox Titrationsp. 78
Other Principles of Titrationp. 81
Summaryp. 82
Introduction to Spectroscopic Methodsp. 83
Electromagnetic Radiationp. 83
Molecules and Electromagnetic Radiationp. 85
Atoms and Electromagnetic Radiationp. 86
Summaryp. 88
UV Spectrophotometryp. 89
Principle of Quantitative Determinationp. 89
Principle of Identificationp. 94
Which Substances Have Strong UV Absorbance?p. 95
Instrumentationp. 95
Practical Work and Method Developmentp. 99
Areas of Usage and Performancep. 101
System Testingp. 101
Summaryp. 102
IR Spectrophotometryp. 103
IR Spectrophotometryp. 103
Instrumentationp. 106
Scopep. 109
Instrument Calibrationp. 109
NIR Spectrophotometryp. 110
Applicationsp. 112
Summaryp. 114
Atomic Spectrometryp. 115
Atomic Absorption Spectrometryp. 115
Instrumentationp. 118
Applications and Performancep. 121
Practical Work and Method Developmentp. 122
Atomic Emission Spectrometryp. 123
Instrumentationp. 124
Summaryp. 124
Chromatographyp. 127
General Principlesp. 127
Retentionp. 131
Column Efficiencyp. 133
Selectivityp. 135
Peak Symmetryp. 136
Resolutionp. 138
Chromatographic Techniquesp. 140
Summaryp. 140
Chromatographic Separation Principlesp. 141
General Introductionp. 141
Normal Phase Chromatographyp. 142
Silicap. 142
Interactionsp. 143
Order of Elutionp. 144
Other Stationary Phasesp. 145
Mobile Phasesp. 146
Summary of Normal Phase Chromatographyp. 147
Reversed Phase Chromatographyp. 148
Stationary Phasesp. 148
Retention Mechanismsp. 150
Mobile Phasesp. 152
Ion-Pair Chromatographyp. 155
Summary of Reversed Phase Chromatographyp. 155
Hydrophilic Interaction Chromatographyp. 156
Chiral Separationsp. 156
Size Exclusion Chromatographyp. 158
Principlep. 158
Summary of SECp. 160
Ion Exchange Chromatographyp. 160
Thin-Layer Chromatographyp. 163
Introductionp. 163
Apparatusp. 164
TLC Platesp. 166
Stationary Phasesp. 166
Mobile Phasesp. 167
Chromatographic Developmentp. 168
Detectionp. 169
Applications of TLCp. 169
Quantitative Analysis and Instrumentationp. 170
Summaryp. 171
High Performance Liquid Chromatographyp. 173
Introductionp. 173
The Chromatographic Separation Processp. 175
The Columnp. 177
Pumpsp. 180
Detectorsp. 182
UV detectorp. 182
Fluorescence Detectorp. 184
Electrochemical Detectorp. 186
Refractive Index, Evaporative Light Scattering and Corona Discharge Detectorsp. 186
Combination of Detectorsp. 187
Injectorsp. 187
Mobile Phasesp. 188
Solvents for Sample Preparationp. 189
Reporting the Resultsp. 189
Summaryp. 190
Gas Chromatographyp. 191
Introductionp. 191
Apparatusp. 192
Temperaturep. 193
Carrier Gasp. 195
Stationary Phasesp. 196
Selectivity in GCp. 197
Columnsp. 198
Capillary Columnsp. 198
Packed Columnsp. 199
Injection Systemsp. 200
Injection Systems for Capillary Columnsp. 200
Injection Systems for Packed Columnsp. 202
Detectorsp. 203
Flame Ionization Detectorp. 203
Nitrogen-Phosphorus Detectorp. 203
Thermal Conductivity Detectorp. 204
Electron Capture Detectorp. 204
Mass Spectrometry Detectorp. 206
Derivatizationp. 206
Silylationp. 206
Alkylationp. 207
Acylationp. 207
The Uses of GCp. 208
More Advanced GC techniquesp. 209
Summaryp. 209
Capillary Electrophoresisp. 211
Principle and Theoryp. 211
Electroosmotic Flowp. 213
Instrumentationp. 214
The Capillaryp. 217
Sample Introductionp. 218
Capillary Zone Electrophoresis; an Examplep. 221
Micellar Electrokinetic Chromatographyp. 222
Chiral Separationsp. 224
Coated Capillariesp. 225
Non-Aqueous CEp. 229
Summaryp. 229
Mass Spectrometryp. 23
Introductionp. 231
Basic Theoryp. 233
Electron Ionizationp. 236
Identification using Electron Ionization Spectrap. 237
Characterization of Totally Unknowns using Electron Ionization Spectrap. 239
Chemical Ionizationp. 244
Electrospray Ionizationp. 246
Atmospheric Pressure Chemical Ionizationp. 247
High-Resolution Mass Spectrometryp. 248
Instrumentationp. 250
Chromatography Coupled with Mass Spectrometryp. 253
Quantitative GC-MS and LC-MSp. 256
Areas of Usage and Performancep. 257
Matrix-Assisted Laser Desorption/Ionization Mass Spectrometryp. 257
Inductively Coupled Plasma Mass Spectrometryp. 258
Summaryp. 259
Miscellaneous Chemical Techniquesp. 261
Potentiometric Determination of Ions using Ion-Selective Electrodesp. 261
Paper Chromatographyp. 263
Supercritical Fluid Chromatographyp. 264
Gel Electrophoresisp. 265
Iso-Electric Focusingp. 267
Nuclear Magnetic Resonance Spectrometryp. 268
Raman Spectrometryp. 270
Sample Preparationp. 273
Why is Sample Preparation Required?p. 273
Main Strategiesp. 274
Recovery and Enrichmentp. 276
Protein Precipitationp. 278
Liquid-Liquid Extractionp. 279
Fundamentalsp. 279
A Closer Look at the Theoryp. 279
Extraction Solventsp. 282
Calculation of Recoveryp. 283
Multiple Extractionsp. 285
LLE with Back-Extractionp. 286
Solid-Liquid Extractionp. 287
Solid Phase Extractionp. 287
Fundamentalsp. 287
The SPE Columnp. 288
Conditioningp. 289
Equipmentp. 290
Reversed-Phase SPEp. 290
Secondary Interactionsp. 292
Ion Exchange SPEp. 293
Mixed-Mode SPEp. 295
Normal-Phase SPEp. 297
Summaryp. 298
Analytical Chemical Characteristics of Selected Drug Substancesp. 299
Amitriptyline and Mianserinp. 299
Morphine and Codeinep. 301
Ibuprofen and Naproxenp. 302
Furosemidep. 304
Paracetamol (Acetaminophen)p. 306
Neutral Drugsp. 307
Quantification and Quality of Analytical Datap. 309
Peak Height and Peak Areap. 309
Calibration Methodsp. 310
External Standard Methodp. 310
Internal Standard Methodp. 313
Standard Additionp. 314
Normalizationp. 314
Validationp. 314
Analytical Procedurep. 317
Accuracyp. 317
Precisionp. 318
Specificityp. 320
Detection Limitp. 320
Quantification Limitp. 321
Linearity and Rangep. 321
Robustnessp. 323
Test Methods in the European Pharmacopeiap. 325
System Suitabilityp. 325
Adjustment of Chromatographic Conditionsp. 326
Chemical Analysis of Drug Substancesp. 327
What is a Pharmaceutical Raw Material, how is it Produced and why must it be Controlled?p. 327
The Pharmacopoeias - the Basis for Control of Pharmaceutical Raw Materialsp. 330
Which Contaminants are Found in Raw Materials, What are the Requirements in a Maximum Content and Why?p. 337
Well Defined Chemical Compoundsp. 339
Mixtures of Organic Compoundsp. 343
How to Check the Identity of Pharmaceutical Raw Materialsp. 344
Overview of the Identification Proceduresp. 344
Techniques used for the Identification of Well Defined Chemical Compoundsp. 344
Infrared Absorption Spectrophotometryp. 344
Ultraviolet and Visible Absorption Spectrophotometryp. 347
Thin-Layer Chromatographyp. 351
Melting Pointp. 352
Polarimetryp. 353
High Performance Liquid Chromatographyp. 356
Chloride and Sulfate Identificationp. 359
How to Test for Impurities in Pharmaceutical Raw Materialsp. 359
Main Purity Tests for Well Defined Chemical Compoundsp. 359
Appearance of Solutionp. 361
Absorbancep. 364
Acidity/Alkalinityp. 365
Optical Rotationp. 365
Related Substancesp. 366
Solvent Residuesp. 372
Foreign Anionsp. 372
Cationic Impuritiesp. 376
Loss on Dryingp. 378
Determination of Waterp. 379
Purity Tests for Raw Materials of the Type of Mixtures of Organic Compoundsp. 382
Oxidizing Substancesp. 383
Acid Valuep. 383
Hydroxyl Valuep. 384
Iodine Valuep. 384
Peroxide Valuep. 385
Saponification Valuep. 385
Unsaponifiable Matterp. 386
Other Testsp. 386
Identification of the Raw Materials of the Type of Mixtures of Organic Compoundsp. 388
How to Determine the Purity of Pharmaceutical Raw Materialsp. 389
Acid-Base Titration in Aqueous Environmentp. 389
Acid-Base Titration in a Non-Aqueous Environmentp. 393
Redox Titrationsp. 396
High Performance Liquid Chromatographyp. 396
UV spectrophotometryp. 401
How to Control Compounds for Which no Pharmacopoeia Monograph Existsp. 402
How are Ph.Eur. and USP Updated?p. 402
Chemical Analysis of Final Pharmaceutical Productsp. 405
Quality Control of Final Pharmaceutical Productsp. 405
Monographs and Chemical Testingp. 406
Identification of the Active Pharmaceutical Ingredientp. 412
Assay of the Active Pharmaceutical Ingredientp. 427
Chemical Tests for Final Pharmaceutical Productsp. 446
Test for Related Substancesp. 446
Uniformity of Contentp. 449
Dissolutionp. 451
Analysis of Drugs in Biological Fluidsp. 453
Introductionp. 453
Drug Developmentp. 453
Therapeutic Drug Monitoringp. 455
Forensic and Toxicological Analysisp. 456
Doping Control Analysisp. 457
The Biological Matrixp. 458
Bioanalytical Methodsp. 460
Samplingp. 460
Sample Preparationp. 461
Protein Precipitationp. 462
Liquid-Liquid Extractionp. 463
Solid-Phase Extractionp. 463
Separationp. 464
Detectionp. 464
Calibration and Quantificationp. 465
Examplesp. 466
Sample Preparationp. 466
Sample Preparation Procedure by LLEp. 466
Comments to the Procedurep. 466
Sample Preparation Procedure by LLE and Back Extractionp. 467
Comments to the Procedurep. 467
Sample Preparation Procedure by SPEp. 467
Comments to the Procedurep. 468
Sample Preparation Procedure by Protein Precipitationp. 468
Comments to the Procedurep. 468
Quantitative Determinationp. 468
Quantitative Determination of Amitriptyline in Serum by LC-MSp. 468
Comments to the Procedurep. 469
Determination of Valproic Acid in Serum by GC-MSp. 471
Comments to the Procedurep. 471
Identificationp. 472
Sample Preparation Procedure for Unknown Screening by Mixed Mode Cation Exchangep. 472
Comments to the Procedurep. 472
GC-MS Procedure for Unknown Screeningp. 473
Comments to the Procedurep. 473
LC-MS-MS Procedure for Unknown Screeningp. 475
Comments to the Procedurep. 475
Indexp. 477
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