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Fundamentals of Analytical Toxicology. Clinical and Forensic. Edition No. 2

  • Book

  • 656 Pages
  • August 2020
  • John Wiley and Sons Ltd
  • ID: 5836553

Fundamentals of Analytical Toxicology is an integrated introduction to the analysis of drugs, poisons, and other foreign compounds in biological and related specimens. Assuming only basic knowledge of analytical chemistry, this invaluable guide helps trainee analytical toxicologists understand the principles and practical skills involved in detecting, identifying, and measuring a broad range of compounds in various biological samples. Clear, easy-to-read chapters provide detailed information on topics including sample collection and preparation, spectrophotometric and luminescence techniques, liquid and gas-liquid chromatography, and mass spectrometry including hyphenated techniques.

This new edition contains thoroughly revised content that reflects contemporary practices and advances in analytical methods. Expanding the scope of the 1995 World Health Organization (WHO) basic analytical toxicology manual, the text includes coverage of separation science, essential pharmacokinetics, xenobiotic absorption, distribution and metabolism, clinical toxicological and substance misuse testing, therapeutic drug monitoring, trace elements and toxic metals analysis, and importantly the clinical interpretation of analytical results.

Written by a prominent team of experienced practitioners, this volume:
  • Focuses on analytical, statistical, and pharmacokinetic principles
  • Describes basic methodology, including colour tests and immunoassay and enzyme-based assays
  • Outlines laboratory operations, such as method validation, quality assessment, staff training, and laboratory accreditation
  • Follows IUPAC nomenclature for chemical names and recommended International Non-proprietary Name (rINN) for drugs and pesticides
  • Includes discussion of 'designer drugs' (novel pharmaceutical substances NPS)

Fundamentals of Analytical Toxicology: Clinical and Forensic, 2nd Edition is an indispensable resource for advanced students and trainee analytical toxicologists across disciplines, such as clinical science, analytical chemistry, forensic science, pathology, applied biology, food safety, and pharmaceutical and pesticide development.

Table of Contents

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

Authors

Robert J. Flanagan Medical Toxicology Unit. Eva Cuypers The London Hospital Medical College, U.K.. Hans H. Maurer University of Saarland, Homburg/Saar, Germany. Robin Whelpton The London Hospital Medical College, U.K..