Fundamentals of Analytical Toxicology

Preface xxiii Health and Safety xxv Nomenclature, Symbols, and Conventions xxvii Uniform Resource Locators xxix Amount Concentration and Mass Concentration xxxi Acknowledgements xxxiii List of Abbreviations xxxv Section A The Basics 1 1 Analytical Toxicology: Overview 3 1.1 Introduction 3 1.2 Modern analytical toxicology 4 1.3 Provision of analytical toxicology services 10 1.4 Applications of analytical toxicology 15 1.5 Summary 21 References 21 2 Sample Collection, Transport, and Storage 23 2.1 Introduction 23 2.2 Clinical samples and sampling 23 2.3 Guidelines for sample collection for analytical toxicology 32 2.4 Sample transport, storage, and disposal 45 2.5 Common interferences 47 2.6 Summary 48 References 48 3 Basic Laboratory Operations 52 3.1 Introduction 52 3.2 Aspects of quantitative analysis 58 3.3 Use of internal standards 74 3.4 Method comparison 78 3.5 Non-parametric statistics 80 3.6 Quality control and quality assessment 84 3.7 Operational considerations 89 3.8 Summary 91 References 91 4 Aspects of Sample Preparation 94 4.1 Introduction 94 4.2 Modes of sample preparation 97 4.3 Plasma protein binding 112 4.4 Hydrolysis of conjugated metabolites 115 4.5 Extraction of drugs from tissues 117 4.6 Summary 117 References 118 5 Colour Tests, and Spectrophotometric and Luminescence Techniques 120 5.1 Introduction 120 5.2 Colour tests in toxicology 120 5.3 Colour tests for pharmaceuticals and illicit drugs 122 5.4 UV/Visible spectrophotometry 123 5.5 Fluorescence and phosphorescence 134 5.6 Chemiluminescence 138 5.7 Infrared and Raman spectroscopy 141 5.8 Summary 143 References 143 6 Immunoassays and Related Assays 145 6.1 Introduction 145 6.2 Basic principles of competitive binding assays 145 6.3 Heterogeneous immunoassays 151 6.4 Homogenous immunoassays 155 6.5 Microparticulate and turbidimetric immunoassays 159 6.6 Assay calibration, quality control, and quality assessment 160 6.7 Interferences and assay failures 162 6.8 Aptamer-based assays 163 6.9 Enzyme-based assays 163 6.10 Summary 165 References 166 Section B Separation Science 167 7 Separation Science: Theoretical Aspects 169 7.1 General introduction 169 7.2 Theoretical aspects of chromatography 170 7.3 Measurement of analyte retention 179 7.4 Summary 181 References 181 8 Planar Chromatography 182 8.1 Introduction 182 8.2 Qualitative thin-layer chromatography 183 8.3 Quantitative thin-layer chromatography 190 8.4 Summary 192 References 192 9 Gas Chromatography 193 9.1 Introduction 193 9.2 Instrumentation 194 9.3 Columns and column packings 203 9.4 Headspace and ‘purge and trap’ analysis 210 9.5 Formation of artefacts in gas chromatography 213 9.6 Derivatization for gas chromatography 213 9.7 Chiral separations 217 9.8 Summary 219 References 220 10 Liquid Chromatography 223 10.1 Introduction 223 10.2 General considerations 224 10.3 Detection in liquid chromatography 232 10.4 Columns and column packings 240 10.5 Modes of liquid chromatography 245 10.6 Chiral separations 250 10.7 Derivatives for liquid chromatography 255 10.8 Use of liquid chromatography in analytical toxicology 256 10.9 Summary 261 References 262 11 Supercritical Fluid Chromatography 264 11.1 Introduction 264 11.2 General considerations 267 11.3 Detection in supercritical fluid chromatography 269 11.4 Columns and column packings 269 11.5 Chiral separations 270 11.6 Toxicological and forensic applications 272 11.7 Summary 273 References 273 12 Capillary Electrophoretic Techniques 275 12.1 Introduction 275 12.2 Theoretical aspects 276 12.3 Sample injection in capillary electrophoresis 280 12.4 Detection in capillary electrophoresis 281 12.5 Other capillary electrokinetic modes 282 12.6 Capillary electrophoretic techniques in analytical toxicology 285 12.7 Summary 287 References 287 13 Mass Spectrometry 289 13.1 Introduction 289 13.2 Instrumentation 291 13.3 Gas chromatography-mass spectrometry 299 13.4 Liquid chromatography-mass spectrometry 304 13.5 Supercritical fluid chromatography-mass spectrometry 308 13.6 Capillary electrophoresis-mass spectrometry 309 13.7 Direct introduction mass spectrometry 310 13.8 Presentation of mass spectral data 315 13.9 Interpretation of mass spectra 317 13.10 Quantitative mass spectrometry 320 13.11 Mass spectrometry imaging 324 13.12 Summary 325 References 325 14 Ion Mobility Spectrometry 329 14.1 Introduction 329 14.2 Theoretical aspects 331 14.3 Types of ion mobility spectrometry 332 14.4 Resolving power 336 14.5 Interfacing ion mobility spectrometry 336 14.6 Applications of ion mobility spectrometry in analytical toxicology 339 14.7 Summary 342 References 342 Section C Essential Pharmacokinetics 345 15 Absorption, Distribution, Metabolism, and Excretion of Xenobiotics 347 15.1 Introduction 347 15.2 Movement of drugs and other xenobiotics around the body 347 15.3 Routes of administration 351 15.4 Distribution 355 15.5 Metabolism 357 15.6 Excretion 371 15.7 Pharmacogenetics and pharmacogenomics 373 15.8 Summary 376 References 377 16 Pharmacokinetics 379 16.1 Introduction 379 16.2 Fundamental concepts 379 16.3 Absorption and elimination 382 16.4 Drug accumulation 384 16.5 Sustained-release preparations 386 16.6 Non-linear pharmacokinetics 387 16.7 Multi-compartment models 390 16.8 Non-compartmental methods 392 16.9 Factors affecting pharmacokinetic parameters 393 16.10 Disease 396 16.11 Pharmacokinetics and the interpretation of results 397 16.12 Summary 402 References 402 Section D Analytical Toxicology 405 17 Toxicology Testing at the Point of Contact 407 17.1 Introduction 407 17.2 Use of point of contact testing 408 17.3 Toxicology testing at the point of contact 412 17.4 Interferences and adulterants 418 17.5 Quality assessment 419 17.6 Summary 419 References 419 18 Laboratory Testing for Substance Misuse 422 18.1 Introduction 422 18.2 Urine testing 425 18.3 Oral fluid testing 433 18.4 Blood testing 437 18.5 Hair testing 438 18.6 Breath testing 445 18.7 Sweat testing 446 18.8 Summary 446 References 447 19 General Analytical Toxicology 452 19.1 Introduction 452 19.2 Gas chromatography 453 19.3 Gas chromatography-mass spectrometry 456 19.4 Liquid chromatography 464 19.5 Liquid chromatography-mass spectrometry 464 19.6 Liquid chromatography-high resolution mass spectrometry 469 19.7 Summary 473 References 475 20 Therapeutic Drug Monitoring 479 20.1 Introduction 479 20.2 Sample collection 480 20.3 Sample types 481 20.4 Analytical methods 483 20.5 Factors affecting interpretation of results 485 20.6 Gazetteer 486 20.7 Summary 499 References 499 21 Trace Elements and Toxic Metals 505 21.1 Introduction 505 21.2 Sample collection and storage 505 21.3 Sample preparation 507 21.4 Atomic spectrometry 509 21.5 Colorimetry and fluorimetry 520 21.6 Electrochemical methods 521 21.7 Catalytic methods 523 21.8 Neutron activation analysis 523 21.9 Chromatographic methods 524 21.10 Quality assessment 525 21.11 Summary 525 References 525 22 Clinical Interpretation of Analytical Results 527 22.1 Introduction 527 22.2 Clinical toxicology 529 22.3 Forensic toxicology 533 22.4 Gazetteer 539 22.5 Sources of further information 574 22.6 Summary 576 References 576 Index 587