Fundamentals of analytical toxicology:
Saved in:
| Format: | Book |
|---|---|
| Language: | English |
| Published: |
Chichester, England
John Wiley & Sons
2007
|
| Subjects: | |
| Online Access: | Table of contents only Publisher description Inhaltsverzeichnis |
| Item Description: | Includes bibliographical references and index |
| Physical Description: | xxxvii, 505 p. Ill., graph. Darst. 26 cm |
| ISBN: | 9780470319345 0470319348 9780470319352 0470319356 |
Staff View
MARC
| LEADER | 00000nam a2200000zc 4500 | ||
|---|---|---|---|
| 001 | BV023324768 | ||
| 003 | DE-604 | ||
| 005 | 00000000000000.0 | ||
| 007 | t | ||
| 008 | 080602s2007 xxkad|| |||| 00||| eng d | ||
| 010 | |a 2007013704 | ||
| 015 | |a GBA753496 |2 dnb | ||
| 020 | |a 9780470319345 |c hb : alk. paper |9 978-0-470-31934-5 | ||
| 020 | |a 0470319348 |c hb : alk. paper |9 0-470-31934-8 | ||
| 020 | |a 9780470319352 |c pbk. : alk. paper |9 978-0-470-31935-2 | ||
| 020 | |a 0470319356 |c pbk. : alk. paper |9 0-470-31935-6 | ||
| 035 | |a (OCoLC)123029273 | ||
| 035 | |a (DE-599)BVBBV023324768 | ||
| 040 | |a DE-604 |b ger |e aacr | ||
| 041 | 0 | |a eng | |
| 044 | |a xxk |c GB | ||
| 049 | |a DE-19 |a DE-Er8 |a DE-20 | ||
| 050 | 0 | |a RA1221 | |
| 082 | 0 | |a 615.9/07 | |
| 084 | |a VT 5300 |0 (DE-625)147745:253 |2 rvk | ||
| 245 | 1 | 0 | |a Fundamentals of analytical toxicology |c Robert J. Flanagan ... [et al.] |
| 264 | 1 | |a Chichester, England |b John Wiley & Sons |c 2007 | |
| 300 | |a xxxvii, 505 p. |b Ill., graph. Darst. |c 26 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Includes bibliographical references and index | ||
| 650 | 4 | |a Analytical toxicology | |
| 650 | 4 | |a Toxicology |x methods | |
| 650 | 4 | |a Chemistry, Clinical |x methods | |
| 650 | 4 | |a Specimen Handling |x methods | |
| 650 | 0 | 7 | |a Toxikologische Analyse |0 (DE-588)4078371-6 |2 gnd |9 rswk-swf |
| 689 | 0 | 0 | |a Toxikologische Analyse |0 (DE-588)4078371-6 |D s |
| 689 | 0 | |5 DE-604 | |
| 700 | 1 | |a Flanagan, Robert J. |e Sonstige |4 oth | |
| 856 | 4 | |u http://www.loc.gov/catdir/toc/ecip0715/2007013704.html |3 Table of contents only | |
| 856 | 4 | |u http://www.loc.gov/catdir/enhancements/fy0739/2007013704-d.html |3 Publisher description | |
| 856 | 4 | 2 | |m HBZ Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016508806&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-016508806 | ||
Record in the Search Index
| _version_ | 1804137665271955456 |
|---|---|
| adam_text | Contents
Preface xix
Health and Safety xxi
Nomenclature, Symbols and Conventions xxiii
Amount Concentration and Mass Concentration xxv
Acknowledgements xxvii
List of Abbreviations xxix
1 Analytical Toxicology: Overview 1
1.1 Introduction 1
1.1.1 Historical development 1
1.2 Modern analytical toxicology 2
1.2.1 Drugs and pesticides 4
1.2.2 Ethanol and other volatile substances 6
1.2.3 Trace elements and toxic metals 7
1.3 Provision of analytical toxicology services 8
1.3.1 Samples and sampling 8
1.3.2 Choice of analytical method 8
1.3.3 Method implementation and validation 9
1.3.4 Quality control and quality assurance 11
1.4 Applications of analytical toxicology 13
1.4.1 Clinical toxicology 13
1.4.2 Forensic toxicology 14
1.4.3 Drug abuse screening 15
1.4.4 Therapeutic drug monitoring (TDM) 16
1.4.5 Occupational and environmental toxicology ] 7
1.5 Summary 18
2 Sample Collection, Transport, and Storage 21
2.1 Introduction 21
2.2 Clinical samples and sampling 21
2.2.1 Health and safety 21
2.2.2 Clinical sample types 23
2.2.2.1 Arterial blood 23
2.2.2.2 Venous blood 23
2.2.2.3 Serum 26
2.2.2.4 Plasma 26
2.2.2.5 Blood cells 27
2.2.2.6 Urine 28
V
vi CONTENTS
2.2.2.7 Stomach contents 28
2.2.2.8 Faeces 28
2.2.2.9 Tissues 29
2.3 Guidelines for sample collection for analytical toxicology 29
2.3.1 Sample collection and preservation 32
2.3.2 Blood (for quantitative work) 32
2.3.3 Blood (for qualitative analysis) 33
2.3.4 Urine 33
2.3.5 Stomach contents 35
2.3.6 Saliva/oral fluids 36
2.3.6.1 Collection devices for saliva/oral fluids 37
2.3.7 Sweat 38
2.3.8 Exhaled air 38
2.3.9 Cerebrospinal fluid 38
2.3.10 Vitreous humour 38
2.3.11 Synovial fluid 39
2.3.12 Liver 39
2.3.13 Other tissues 39
2.3.14 Insect larvae 39
2.3.15 Keratinaceous tissues (hair and nail) 40
2.3.16 Bone and bone marrow 41
2.3.17 Injection sites 41
2.3.18 Scene residues 41
2.4 Sample transport and storage 42
2.5 Common interferences 44
2.6 Summary 45
3 Sample Preparation 49
3.1 Introduction 49
3.2 Modes of sample preparation 51
3.2.1 Direct analysis/on-line sample preparation 51
3.2.2 Protein preciptation 52
3.2.3 Microdiffusion 54
3.2.4 Headspace and purge-and-trap analysis 55
3.2.5 Liquid-liquid extraction 57
3.2.5.1 Theory of pH-comrolled liquid-liquid extraction 53
3.2.5.2 Ion-pair extraction 66
3.2.5.3 Liquid-liquid extraction columns 67
3.2.6 Solid-phase extraction 67
3.2.7 Solid-phase microextraction 73
3.2.8 Liquid-phase microextraction 76
3.2.9 Supercritical fluid extraction 77
3.2.10 Accelerated solvent extraction 7g
3.3 Measurement of nonbound plasma concentrations 79
3.3.1 Ultrafiltration 80
3.3.2 Equilibrium dialysis gi
CONTENTS vii
3.4 Hydrolysis of conjugated metabolites 82
3.5 Extraction of drugs from tissues 84
3.5.1 Hair analysis for drugs and organic poisons 85
3.6 Derivatization 87
3.7 Summary 88
4 Colour Tests, and Spectrophotometric and Luminescence Techniques 95
4.1 Introduction 95
4.1.1 Historical development 95
4.2 Colour tests 96
4.3 UV/visible spectrophotometry 97
4.3.1 The Beer-Lambert law 98
4.3.2 Instrumentation 100
4.3.2.1 Derivative spectrophotometry 102
4.3.3 Spectrophotometric assays 104
4.3.3.1 Salicylates in plasma or urine 106
4.3.3.2 Carboxyhaemoglobin (COHb) in whole blood 106
4.3.3.3 Cyanide in whole blood by microdiffusion 107
4.3.3.4 Colorimetric measurement of sulfonamides 108
4.4 Luminescence 108
4.4.1 Fluorescence and phosphorescence 108
4.4.1.1 Intensity of fluorescence and quantum yield 109
4.4.1.2 Instrumentation 1 10
4.4.1.3 Fluorescence assays 1 ]
4.4.2 Chemiluminescence 112
4.4.2.1 Instrumentation ] 14
4.4.2.2 Chemiluminescence assays ] 14
4.5 Summary 115
5 Introduction to Chromatography and Capillary Electrophoresis 117
5.1 General introduction 117
5.1.1 Historical development 117
5.2 Theoretical aspects of chromatography 119
5.2.1 Analyte phase distribution 119
5.2.2 Column efficiency 121
5.2.3 Zone broadening 122
5.2.3.1 Multiple path and eddy diffusion 122
5.2.3.2 Longitudinal diffusion 123
5.2.3.3 Resistance to mass transfer ] 23
5.2.4 Extra-column contributions to zone broadening 125
5.2.5 Temperature programming and gradient elution 125
5.2.6 Selectivity 126
5.2.7 Peak asymmetry 127
5.3 Measurement of analyte retention 128
5.4 Summary 129
viii CONTENTS
6 Thin-Layer Chromatography 131
6.1 Introduction 131
6.2 Preparation of thin-layer plates 132
6.3 Sample application 133
6.4 Developing the chromatogram 133
6.5 Visualizing the chromatogram 135
6.6 Retention factor (Rf) 137
6.7 Toxi-Lab 140
6.8 High-performance thin-layer chromatography 140
6.8.1 Forced-flow planar chromatography 141
6.9 Quantitative thin-layer chromatography 141
6.10 Summary 142
7 Gas Chromatography 145
7.1 Introduction 145
7.2 Instrumentation 146
7.2.1 Injectors and injection technique 147
7.2.1.1 Cryofocusing/thermal desorption 148
7.2.2 Detectors for GC 149
7.2.2.1 Thermal-conductivity detection 150
7.2.2.2 Flame-ionization detection 150
7.2.2.3 Nitrogen-phosphorus detection 151
7.2.2.4 Electron capture detection 152
7.2.2.5 Pulsed-discharge detection 154
7.2.2.6 Flame-photometric detection 155
7.2.2.7 Atomic-emission detection 155
7.2.2.8 Fourier-transform infrared detection 156
7.3 Columns and column packings 156
7.3.1 Packed columns 157
7.3.2 Capillary columns 160
7.3.3 Multidimensional GC 163
7.4 Derivatization for GC 164
7.4.1 Electron-capturing derivatives 165
7.5 Chiral separations 166
7.6 Applications of gas chromatography in analytical toxicology 167
7.6.1 Systematic toxicological analysis 167
7.6.2 Quantitative analysis of drugs and other poisons 179
7.6.2.1 Measurement of carbon monoxide and cyanide 1JQ
7.6.2.2 Measurement of ethanol and other volatiles J 70
7.7 Summary 173
8 High-Performance Liquid Chromatography 177
8.1 Introduction J77
CONTENTS ix
8.2 HPLC: general considerations 178
8.2.1 The column 179
8.2.1.1 Column oven 180
8.2.2 Theeluent 181
8.2.3 The pump 182
8.2.4 Sample introduction 184
8.2.5 System operation 185
8.3 Detection in HPLC 186
8.3.1 UV/visible absorption detection 188
8.3.2 Fluorescence detection 189
8.3.3 Chemiluminescence detection 189
8.3.4 Electrochemical detection 190
8.3.5 Chemiluminescent nitrogen detection 192
8.3.6 Evaporative light scattering detection 193
8.3.7 Charged aerosol detection 193
8.3.8 Radioactivity detection 194
8.3.9 Chiral detection 195
8.3.10 Post-column modification 195
8.3.11 Immunoassay detection 196
8.4 Columns and column packings 196
8.4.1 Column configuration 197
8.4.2 Column packings 197
8.4.2.1 Chemical modification of silica 198
8.4.2.2 Bonded-phase selection 199
8.4.2.3 Stability of silica packings 200
8.4.2.4 Monolithic columns 200
8.4.2.5 Hybrid particle columns 201
8.5 Modes of HPLC 202
8.5.1 Normal-phase chromatography 202
8.5.2 Reversed-phase chromatography 202
8.5.3 Ion-exchange chromatography 203
8.5.4 Ion-pair chromatography 204
8.5.5 Size-exclusion chromatography 204
8.5.6 Affinity chromatography 205
8.5.7 Semipreparative and preparative chromatography 206
8.6 Chiral separations 207
8.6.1 Chiral stationary phases 208
8.6.1.1 Amylose and cellulose polymers 208
8.6.1.2 Crown ethers 208
8.6.1.3 Cyclodextrins 209
8.6.1.4 Ligand-exchange chromatography 210
8.6.1.5 Macrocyclic glycopeptides 210
8.6.1.6 Pirkle brush-type phases 211
8.6.1.7 Protein-based phases 213
8.6.2 Chiral eluent additives 213
X CONTENTS
8.7 Derivatives for HPLC 214
8.7.1 Fluorescent derivatives 214
8.7.2 Electroactive derivatives 215
8.7.3 Chiral derivatives 215
8.8 Use of HPLC in analytical toxicology 216
8.8.1 Acidic and neutral compounds 216
8.8.2 Basic drugs and quaternary ammonium compounds 217
8.8.2.1 Nonaqueous ionic eluent systems 219
8.8.3 Systematic toxicological analysis 222
8.8.4 Chiral analyses 224
8.9 Summary 224
9 Capillary Electrophoretic Techniques 231
9.1 Introduction 231
9.2 Electrophoretic mobility 232
9.3 Efficiency and zone broadening 234
9.3.1 Joule heating 235
9.3.2 Electrodispersion 235
9.3.3 Adsorption of analyte onto the capillary wall 236
9.4 Sample injection 236
9.4.1 Hydrodynamic injection 236
9.4.2 Electrokinetic injection 237
9.4.3 Sample stacking 237
9.5 Detection 237
9.6 Reproducibility of migration time 239
9.7 Applications of capillary electrophoresis 240
9.8 Micellar electrokinetic capillary chromatography 240
9.9 Other capillary electrokinetic modes 242
9.9.1 Capillary electrochromatography 242
9.9.2 Capillary gel electrophoresis 244
9.9.3 Capillary isoelectric focusing 244
9.10 CE techniques in analytical toxicology 244
9.11 Chiral separations 244
9.12 Summary 246
10 Mass Spectrometry 249
10.1 Introduction 249
10.1.1 Historical development 250
10.2 Instrumentation 251
10.2.1 Sector instruments 252
10.2.2 Quadrupole instruments 253
10.2.3 Quadrupole ion-trap instruments 253
10.2.4 Ion cyclotron resonance 254
CONTENTS xi
10.2.5 Controlled fragmentation (MS-MS) 254
10.3 Presentation of mass spectral data 255
10.4 Gas chromatography-mass spectrometry 256
10.4.1 Electron ionization 258
10.4.2 Chemical ionization 259
10.4.3 Application in analytical toxicology 260
10.5 Liquid chromatography-mass spectrometry 266
10.5.1 Atmospheric-pressure chemical ionization 268
10.5.2 Atmospheric-pressure photoionization 269
10.5.3 Electrospray or ionspray ionization 269
10.5.4 Flow fast-atom bombardment ionization 271
10.5.5 Particle-beam ionization 271
10.5.6 Thermospray 271
10.5.7 Application in analytical toxicology 272
10.6 Interpretation of mass spectra 274
10.7 Quantitative mass spectrometry 277
10.8 Summary 278
11 Trace Elements and Toxic Metals 281
11.1 Introduction 281
11.1.1 Historical development 281
11.2 Sample collection and storage 282
11.3 Sample preparation 284
11.3.1 Analysis of tissues 285
11.3.2 Analyte enrichment 285
11.4 Atomic spectrometry 286
11.4.1 General principles of AES, AAS and AFS 286
11.4.2 Atomic absorption spectrometry 287
11.4.2.1 Flame atomization 288
11.4.2.2 Electrothermal atomization 289
11.4.2.3 Sources of error 290
11.4.3 Atomic emission and atomic fluorescence spectrometry 292
11.4.3.1 Atomic emission spectrometry 292
11.4.3.2 Atomic fluorescence spectrometry 293
11.4.4 Inductively coupled plasma-mass spectrometry 293
11.4.4.1 Ion sources 294
11.4.4.2 Mass analyzers 294
11.4.4.3 Interferences 294
11.4.5 Vapour generation approaches 295
11.4.5.1 Hydride generation 295
11.4.5.2 Mercury vapour generation 296
11.4.6 X-ray fluorescence 297
11.5 Colorimetry and fluorimetry 298
Xii CONTENTS
11.6 Electrochemical methods 299
11.6.1 Anodic stripping voltammetry 299
11.6.2 Ion-selective electrodes 300
11.7 Catalytic methods 301
11.8 Neutron activation analysis 302
11.9 Chromatographic methods 302
11.9.1 Chromatography 302
11.9.2 Speciation 303
11.10 Quality assurance 303
11.11 Summary 304
12 Immunoassays and Enzyme-Based Assays 309
12.1 Introduction 309
12.1.1 Historical development 309
12.2 Basic principles of competitive binding assays 310
12.2.1 Antibody formation 310
12.2.2 Specificity 311
12.2.3 Performing the assay 313
12.2.3.1 Classical radioimmunoassay 313
12.2.3.2 Modern radioimmunoassay (RIA) 315
12.2.4 Non-isotopic immunoassay 315
12.2.5 Assay sensitivity and selectivity 316
12.2.6 Immunoassay development 317
12.2.7 Radioreceptor assays 318
12.3 Heterogeneous immunoassays 318
12.3.1 Tetramefhylbenzidine reporter system 318
12.3.2 Antigen-labelled competitive ELISA 319
12.3.3 Antibody-labelled competitive ELISA 320
12.3.4 Sandwich ELISA 320
12.3.5 Lateral flow competitive ELISA 321
12.3.6 Chemiluminescent immunoassays (CLIA) 321
12.4 Homogenous immunoassays 321
12.4.1 Enzyme-multiplied immunoassay technique (EMIT) 321
12.4.2 Fluorescence polarization immunoassay (FPIA) 323
12.4.3 Cloned enzyme donor immunoassay (CEDIA) 324
12.5 Microparticulate and turbidimetric immunoassays 326
12.5.1 Microparticle enzyme immunoassay (MEIA) 326
12.5.2 Chemiluminescent magnetic immunoassay (CMIA) 327
12.6 Assay calibration, quality control and quality assurance 327
12.6.1 Immunoassay calibration 327
12.6.2 Drug screening 329
12.7 Interferences and assay failures 329
12.7.1 Digoxin 33Q
12.7.1.1 Digoxin-like immunoreactive substances (DLIS) 339
12.7.1.2 Other digoxin-like immunoreactive substances 331
CONTENTS xiii
12.7.1.3 Measurement of plasma digoxin after Fab antibody fragment
administration 331
12.7.2 Insulin and C-peptide 331
12.8 Enzyme-based assays 332
12.8.1 Paracetamol 332
12.8.2 Ethanol 333
12.8.3 Anticholinesterases 334
12.9 Summary 334
13 Toxicology Testing at the Point of Care 339
13.1 Introduction 339
13.1.1 Historical development 340
13.2 UseofPOCT 340
13.2.1 Samples and sample collection 341
13.3 Analytes 343
13.3.1 Ethanol 343
13.3.1.1 Breath ethanol 343
13.3.1.2 Saliva ethanol 343
13.3.2 Drugs of abuse 344
13.3.2.1 Urine testing 345
13.3.2.2 Oral fluid testing 346
13.3.2.3 Sweat testing 346
13.3.3 Paracetamol and salicylates 346
13.3.4 Snake envenomation 347
13.3.5 Therapeutic drug monitoring 347
13.3.5.1 Lithium 348
13.3.5.2 Theophylline 348
13.3.5.3 Anticonvulsants 348
13.4 Interferences and adulterants 348
13.5 Quality assurance 349
13.6 Summary 350
14 Basic Laboratory Operations 353
14.1 Introduction 353
14.1.1 Reagents and standard solutions 354
14.1.2 Reference compounds 354
14.1.3 Preparation and storage of calibration solutions 356
14.2 Aspects of quantitative analysis 358
14.2.1 Analytical error 358
14.2.1.1 Confidence intervals 360
14.2.2 Minimizing random errors 361
14.2.2.1 Preparation of a solution of known concentration 362
14.2.3 Accuracy and Precision 362
14.2.3.1 Assessing precision and accuracy 363
xiv CONTENTS
14.2.3.2 Detecting systematic error (fixed bias) 363
14.2.3.3 Identifying sources of variation: analysis of variance 364
14.2.4 Calibration graphs 365
14.2.4.1 Linear regression 366
14.2.4.2 Testing for linearity 368
14.2.4.3 Weighted linear regression 370
14.2.4.4 Nonlinear calibration curves 370
14.2.4.5 Residuals and standardized residuals 372
14.2.4.6 Blank samples and the intercept 372
14.2.4.7 Method of standard additions 373
14.2.4.8 Limits of detection and quantitation 373
14.2.4.9 Curve fitting and choice of equation 374
14.2.4.10 Single point calibration 375
14.2.5 Batch analyses 375
14.3 Use of internal standards 376
14.3.1 Advantages of internal standardization 378
14.3.1.1 Reproducibility of injection volume 378
14.3.1.2 Instability of the detection system 379
14.3.1.3 Pipetting errors and evaporation of extraction solvent 379
14.3.1.4 Extraction efficiency 380
14.3.1.5 Derivatization and nonstoichiometric reactions 381
14.3.2 Internal standard availability 381
14.3.3 Potential disadvantages of internal standardization 382
14.4 Method comparison 382
14.4.1 Bland-Altman plots 383
14.5 Nonparametric statistics 384
14.5.1 Sign Tests 385
14.5.1.1 Wilcoxon signed rank test 386
14.5.2 Runs test 387
14.5.3 Mann-Whitney £/-test 387
14.5.4 Spearman rank correlation 387
14.5.5 Nonparametric regression 388
14.6 Quality control and proficiency testing 389
14.6.1 Quality control charts 390
14.6.1.1 Shewhart charts 390
14.6.1.2 Cusum charts 390
14.6.1.3 J-chart 39
14.6.1.4 Westgard rules 392
14.6.2 External quality assurance 392
14.7 Operational considerations 393
14.7.1 Staff training 393
14.7.2 Recording and reporting results 394
14.7.3 Toxicology EQA schemes 395
14.8 Summary 39-7
CONTENTS xv
15 Absorption, Distribution, Metabolism and Excretion of Xenobiotic
Compounds 399
15.1 Introduction 339
15.1.1 Historical development 399
15.2 Routes of administration 400
15.2.1 Oral dosage 400
15.2.1.1 P-Glycoprotein 402
15.2.1.2 Presystemic metabolism 403
15.2.2 Intravenous injection 403
15.2.3 Intramuscular and subcutaneous injection 404
15.2.4 Sublingual and rectal administration 404
15.2.5 Intranasal administration 405
15.2.6 Transdermal administration 405
15.2.7 Inhalation 405
15.2.8 Other routes of administration 405
15.3 Absorption 406
15.3.1 Passive diffusion 406
15.3.1.1 Partition coefficient 407
15.3.1.2 Ionization 407
15.3.2 Carrier-mediated absorption 408
15.3.3 Absorption from muscle and subcutaneous tissue 409
15.4 Distribution 409
15.4.1 Ion trapping 410
15.4.2 Binding to macromolecules 411
15.4.2.1 Plasma protein binding 411
15.4.3 Distribution in lipid 412
15.4.4 Active transport 412
15.5 Metabolism 412
15.5.1 Phase 1 metabolism 413
15.5.1.1 The cytochrome P450 family 413
15.5.1.2 Other phase 1 oxidases 414
15.5.1.3 Microsomal reductions 416
15.5.1.4 Hydrolysis 416
15.5.2 Phase 2 reactions 417
15.5.2.1 D-Glucuronidation 417
15.5.2.2 O-sulfation and W-acetylation 418
15.5.2.3 O-, N- and S-methylation 419
15.5.2.4 Conjugation with glutathione 419
15.5.2.5 Amino acid conjugation 419
15.5.3 Metabolic reactions of analytical or toxicological importance 420
15.5.3.1 Oxidative dealkylation 420
15.5.3.2 Hydroxylation 421
15.5.3.3 S- and N-oxidation 422
15.5.3.4 Oxidative dehalogenation 423
xvi CONTENTS
15.5.3.5 Desulftiration 425
15.5.3.6 Trans-sulfuration and trans-esterification 425
15.6 Excretion 425
15.6.1 The kidney 426
15.6.1.1 Tubular secretion 427
15.6.1.2 Excretion of metabolites 427
15.6.2 Biliary excretion 427
15.6.2.1 Enterohepatic recirculation 427
15.7 Summary 428
16 Pharmacokinetics 431
16.1 Introduction 431
16.1.1 Historical development 431
16.1.2 Symbols and conventions 432
16.2 Fundamental concepts 432
16.2.1 Rates, rate constants and reaction order 432
16.2.1.1 First-order elimination 433
16.2.1.2 Zero-order elimination 434
16.2.2 Dependence of half-life on volume of distribution
and clearance 434
16.2.2.1 Apparent volume of distribution 435
16.2.2.2 Organ clearance 435
16.2.2.3 Whole body clearance 436
16.3 Absorption and elimination 437
16.3.1 First-order absorption 437
16.3.2 Bioavailability 438
16.3.3 Maximum concentration (Cmax) 439
16.4 Drug accumulation 439
16.4.1 Intravenous infusion 439
16.4.1.1 Loading doses 440
16.4.2 Multiple dosage 440
16.5 Sustained-release preparations 441
16.5.1 Intramuscular depot injection 442
16.5.2 Other sustained-release preparations 443
16.6 Non-linear pharmacokinetics 443
16.6.1 Ethanol 445
16.7 Multicompartment models 447
16.7.1 Calculation of rate constants 449
16.7.2 Volumes of distribution in a two-compartment model 450
16.8 Model-independent pharmacokinetic parameters 451
16.8.1 Apparent volume of distribution 452
16.8.2 Clearance 453
16.8.3 Model-independent approach 453
16.9 Pharmacokinetics and the interpretation of results 454
16.9.1 Back-calculation of dose or time of dose 454
CONTENTS xvii
16.9.1.1 How much substance was administered? 455
16.9.1.2 When was the substance administered? 455
16.9.1.3 Practical examples 455
16.9.1.4 Calculation of time of cannabis exposure 455
16.9.2 Toxicokinetics 458
16.10 Summary 461
17 Clinical Interpretation of Analytical Results 463
17.1 Introduction 463
17.2 Pharmacogenetics 463
17.2.1 Acetylator status 465
17.2.1.1 Isoniazid 465
17.2.1.2 Sulfonamides 465
17.2.2 Cytochrome P450 polymorphisms 466
17.2.2.1 CYP2D6 polymorphism 466
17.2.2.2 CYP2C9 and CYP2C19 polymorphisms 467
17.2.2.3 Other CYP polymorphisms 467
17.2.3 Atypical cholinesterase 467
17.2.4 Glucose-6-phosphate dehydrogenase (G6PD) 468
17.2.5 Alcohol dehydrogenase and aldehyde dehydrogenase 468
17.3 Effects of age, sex and disease on drug disposition 468
17.3.1 Age 468
17.3.1.1 Effect of age on renal function 469
17.3.2 Disease 469
17.3.3 Sex 470
17.4 Enzyme induction and inhibition 471
17.4.1 Enzyme induction 471
17.4.2 Enzyme inhibition 472
17.5 Investigation of acute poisoning 472
17.5.1 Selectivity and reliability of analytical methods 474
17.5.2 Route and duration of exposure and mechanism of toxicity 474
17.5.3 Hair analysis 476
17.5.4 Sources of further information 477
17.6 Postmortem toxicology 478
17.6.1 Choice of sample and sample collection site 479
17.6.2 Assay calibration 480
17.6.3 Interpretation of analytical results 481
17.7 Gazetteer 483
17.7.1 Antidepressants 483
17.7.2 Anti-epileptics and antipsychotics 483
17.7.3 Carbon monoxide and cyanide 483
17.7.4 Cannabis 484
17.7.5 Cardioactive drugs 485
17.7.6 Cocaine 485
17.7.7 Drug-facilitated sexual assault 486
xviii CONTENTS
17.7.8 Ethanol (ethyl alcohol, alcohol ) 487
17.7.9 Heroin/morphine 488
17.7.10 Hypoglycaemic agents 489
17.7.11 Methadone 489
17.7.12 Methylenedioxymetamfetamine and related compounds 490
17.7.13 Volatile substance abuse (VSA) 490
17.8 Summary 490
Index 495
|
| adam_txt |
Contents
Preface xix
Health and Safety xxi
Nomenclature, Symbols and Conventions xxiii
Amount Concentration and Mass Concentration xxv
Acknowledgements xxvii
List of Abbreviations xxix
1 Analytical Toxicology: Overview 1
1.1 Introduction 1
1.1.1 Historical development 1
1.2 Modern analytical toxicology 2
1.2.1 Drugs and pesticides 4
1.2.2 Ethanol and other volatile substances 6
1.2.3 Trace elements and toxic metals 7
1.3 Provision of analytical toxicology services 8
1.3.1 Samples and sampling 8
1.3.2 Choice of analytical method 8
1.3.3 Method implementation and validation 9
1.3.4 Quality control and quality assurance 11
1.4 Applications of analytical toxicology 13
1.4.1 Clinical toxicology 13
1.4.2 Forensic toxicology 14
1.4.3 Drug abuse screening 15
1.4.4 Therapeutic drug monitoring (TDM) 16
1.4.5 Occupational and environmental toxicology ] 7
1.5 Summary 18
2 Sample Collection, Transport, and Storage 21
2.1 Introduction 21
2.2 Clinical samples and sampling 21
2.2.1 Health and safety 21
2.2.2 Clinical sample types 23
2.2.2.1 Arterial blood 23
2.2.2.2 Venous blood 23
2.2.2.3 Serum 26
2.2.2.4 Plasma 26
2.2.2.5 Blood cells 27
2.2.2.6 Urine 28
V
vi CONTENTS
2.2.2.7 Stomach contents 28
2.2.2.8 Faeces 28
2.2.2.9 Tissues 29
2.3 Guidelines for sample collection for analytical toxicology 29
2.3.1 Sample collection and preservation 32
2.3.2 Blood (for quantitative work) 32
2.3.3 Blood (for qualitative analysis) 33
2.3.4 Urine 33
2.3.5 Stomach contents 35
2.3.6 Saliva/oral fluids 36
2.3.6.1 Collection devices for saliva/oral fluids 37
2.3.7 Sweat 38
2.3.8 Exhaled air 38
2.3.9 Cerebrospinal fluid 38
2.3.10 Vitreous humour 38
2.3.11 Synovial fluid 39
2.3.12 Liver 39
2.3.13 Other tissues 39
2.3.14 Insect larvae 39
2.3.15 Keratinaceous tissues (hair and nail) 40
2.3.16 Bone and bone marrow 41
2.3.17 Injection sites 41
2.3.18 'Scene residues' 41
2.4 Sample transport and storage 42
2.5 Common interferences 44
2.6 Summary 45
3 Sample Preparation 49
3.1 Introduction 49
3.2 Modes of sample preparation 51
3.2.1 Direct analysis/on-line sample preparation 51
3.2.2 Protein preciptation 52
3.2.3 Microdiffusion 54
3.2.4 Headspace and 'purge-and-trap' analysis 55
3.2.5 Liquid-liquid extraction 57
3.2.5.1 Theory of pH-comrolled liquid-liquid extraction 53
3.2.5.2 Ion-pair extraction 66
3.2.5.3 Liquid-liquid extraction columns 67
3.2.6 Solid-phase extraction 67
3.2.7 Solid-phase microextraction 73
3.2.8 Liquid-phase microextraction 76
3.2.9 Supercritical fluid extraction 77
3.2.10 Accelerated solvent extraction 7g
3.3 Measurement of nonbound plasma concentrations 79
3.3.1 Ultrafiltration 80
3.3.2 Equilibrium dialysis gi
CONTENTS vii
3.4 Hydrolysis of conjugated metabolites 82
3.5 Extraction of drugs from tissues 84
3.5.1 Hair analysis for drugs and organic poisons 85
3.6 Derivatization 87
3.7 Summary 88
4 Colour Tests, and Spectrophotometric and Luminescence Techniques 95
4.1 Introduction 95
4.1.1 Historical development 95
4.2 Colour tests 96
4.3 UV/visible spectrophotometry 97
4.3.1 The Beer-Lambert law 98
4.3.2 Instrumentation 100
4.3.2.1 Derivative spectrophotometry 102
4.3.3 Spectrophotometric assays 104
4.3.3.1 Salicylates in plasma or urine 106
4.3.3.2 Carboxyhaemoglobin (COHb) in whole blood 106
4.3.3.3 Cyanide in whole blood by microdiffusion 107
4.3.3.4 Colorimetric measurement of sulfonamides 108
4.4 Luminescence 108
4.4.1 Fluorescence and phosphorescence 108
4.4.1.1 Intensity of fluorescence and quantum yield 109
4.4.1.2 Instrumentation 1 10
4.4.1.3 Fluorescence assays 1 \ ]
4.4.2 Chemiluminescence 112
4.4.2.1 Instrumentation ] 14
4.4.2.2 Chemiluminescence assays ] 14
4.5 Summary 115
5 Introduction to Chromatography and Capillary Electrophoresis 117
5.1 General introduction 117
5.1.1 Historical development 117
5.2 Theoretical aspects of chromatography 119
5.2.1 Analyte phase distribution 119
5.2.2 Column efficiency 121
5.2.3 Zone broadening 122
5.2.3.1 Multiple path and eddy diffusion 122
5.2.3.2 Longitudinal diffusion 123
5.2.3.3 Resistance to mass transfer ] 23
5.2.4 Extra-column contributions to zone broadening 125
5.2.5 Temperature programming and gradient elution 125
5.2.6 Selectivity 126
5.2.7 Peak asymmetry 127
5.3 Measurement of analyte retention 128
5.4 Summary 129
viii CONTENTS
6 Thin-Layer Chromatography 131
6.1 Introduction 131
6.2 Preparation of thin-layer plates 132
6.3 Sample application 133
6.4 Developing the chromatogram 133
6.5 Visualizing the chromatogram 135
6.6 Retention factor (Rf) 137
6.7 Toxi-Lab 140
6.8 High-performance thin-layer chromatography 140
6.8.1 Forced-flow planar chromatography 141
6.9 Quantitative thin-layer chromatography 141
6.10 Summary 142
7 Gas Chromatography 145
7.1 Introduction 145
7.2 Instrumentation 146
7.2.1 Injectors and injection technique 147
7.2.1.1 Cryofocusing/thermal desorption 148
7.2.2 Detectors for GC 149
7.2.2.1 Thermal-conductivity detection 150
7.2.2.2 Flame-ionization detection 150
7.2.2.3 Nitrogen-phosphorus detection 151
7.2.2.4 Electron capture detection 152
7.2.2.5 Pulsed-discharge detection 154
7.2.2.6 Flame-photometric detection 155
7.2.2.7 Atomic-emission detection 155
7.2.2.8 Fourier-transform infrared detection 156
7.3 Columns and column packings 156
7.3.1 Packed columns 157
7.3.2 Capillary columns 160
7.3.3 Multidimensional GC 163
7.4 Derivatization for GC 164
7.4.1 Electron-capturing derivatives 165
7.5 Chiral separations 166
7.6 Applications of gas chromatography in analytical toxicology 167
7.6.1 Systematic toxicological analysis 167
7.6.2 Quantitative analysis of drugs and other poisons 179
7.6.2.1 Measurement of carbon monoxide and cyanide 1JQ
7.6.2.2 Measurement of ethanol and other volatiles J 70
7.7 Summary 173
8 High-Performance Liquid Chromatography 177
8.1 Introduction J77
CONTENTS ix
8.2 HPLC: general considerations 178
8.2.1 The column 179
8.2.1.1 Column oven 180
8.2.2 Theeluent 181
8.2.3 The pump 182
8.2.4 Sample introduction 184
8.2.5 System operation 185
8.3 Detection in HPLC 186
8.3.1 UV/visible absorption detection 188
8.3.2 Fluorescence detection 189
8.3.3 Chemiluminescence detection 189
8.3.4 Electrochemical detection 190
8.3.5 Chemiluminescent nitrogen detection 192
8.3.6 Evaporative light scattering detection 193
8.3.7 Charged aerosol detection 193
8.3.8 Radioactivity detection 194
8.3.9 Chiral detection 195
8.3.10 Post-column modification 195
8.3.11 Immunoassay detection 196
8.4 Columns and column packings 196
8.4.1 Column configuration 197
8.4.2 Column packings 197
8.4.2.1 Chemical modification of silica 198
8.4.2.2 Bonded-phase selection 199
8.4.2.3 Stability of silica packings 200
8.4.2.4 Monolithic columns 200
8.4.2.5 Hybrid particle columns 201
8.5 Modes of HPLC 202
8.5.1 Normal-phase chromatography 202
8.5.2 Reversed-phase chromatography 202
8.5.3 Ion-exchange chromatography 203
8.5.4 Ion-pair chromatography 204
8.5.5 Size-exclusion chromatography 204
8.5.6 Affinity chromatography 205
8.5.7 Semipreparative and preparative chromatography 206
8.6 Chiral separations 207
8.6.1 Chiral stationary phases 208
8.6.1.1 Amylose and cellulose polymers 208
8.6.1.2 Crown ethers 208
8.6.1.3 Cyclodextrins 209
8.6.1.4 Ligand-exchange chromatography 210
8.6.1.5 Macrocyclic glycopeptides 210
8.6.1.6 Pirkle brush-type phases 211
8.6.1.7 Protein-based phases 213
8.6.2 Chiral eluent additives 213
X CONTENTS
8.7 Derivatives for HPLC 214
8.7.1 Fluorescent derivatives 214
8.7.2 Electroactive derivatives 215
8.7.3 Chiral derivatives 215
8.8 Use of HPLC in analytical toxicology 216
8.8.1 Acidic and neutral compounds 216
8.8.2 Basic drugs and quaternary ammonium compounds 217
8.8.2.1 Nonaqueous ionic eluent systems 219
8.8.3 Systematic toxicological analysis 222
8.8.4 Chiral analyses 224
8.9 Summary 224
9 Capillary Electrophoretic Techniques 231
9.1 Introduction 231
9.2 Electrophoretic mobility 232
9.3 Efficiency and zone broadening 234
9.3.1 Joule heating 235
9.3.2 Electrodispersion 235
9.3.3 Adsorption of analyte onto the capillary wall 236
9.4 Sample injection 236
9.4.1 Hydrodynamic injection 236
9.4.2 Electrokinetic injection 237
9.4.3 Sample 'stacking' 237
9.5 Detection 237
9.6 Reproducibility of migration time 239
9.7 Applications of capillary electrophoresis 240
9.8 Micellar electrokinetic capillary chromatography 240
9.9 Other capillary electrokinetic modes 242
9.9.1 Capillary electrochromatography 242
9.9.2 Capillary gel electrophoresis 244
9.9.3 Capillary isoelectric focusing 244
9.10 CE techniques in analytical toxicology 244
9.11 Chiral separations 244
9.12 Summary 246
10 Mass Spectrometry 249
10.1 Introduction 249
10.1.1 Historical development 250
10.2 Instrumentation 251
10.2.1 Sector instruments 252
10.2.2 Quadrupole instruments 253
10.2.3 Quadrupole ion-trap instruments 253
10.2.4 Ion cyclotron resonance 254
CONTENTS xi
10.2.5 Controlled fragmentation (MS-MS) 254
10.3 Presentation of mass spectral data 255
10.4 Gas chromatography-mass spectrometry 256
10.4.1 Electron ionization 258
10.4.2 Chemical ionization 259
10.4.3 Application in analytical toxicology 260
10.5 Liquid chromatography-mass spectrometry 266
10.5.1 Atmospheric-pressure chemical ionization 268
10.5.2 Atmospheric-pressure photoionization 269
10.5.3 Electrospray or ionspray ionization 269
10.5.4 Flow fast-atom bombardment ionization 271
10.5.5 Particle-beam ionization 271
10.5.6 Thermospray 271
10.5.7 Application in analytical toxicology 272
10.6 Interpretation of mass spectra 274
10.7 Quantitative mass spectrometry 277
10.8 Summary 278
11 Trace Elements and Toxic Metals 281
11.1 Introduction 281
11.1.1 Historical development 281
11.2 Sample collection and storage 282
11.3 Sample preparation 284
11.3.1 Analysis of tissues 285
11.3.2 Analyte enrichment 285
11.4 Atomic spectrometry 286
11.4.1 General principles of AES, AAS and AFS 286
11.4.2 Atomic absorption spectrometry 287
11.4.2.1 Flame atomization 288
11.4.2.2 Electrothermal atomization 289
11.4.2.3 Sources of error 290
11.4.3 Atomic emission and atomic fluorescence spectrometry 292
11.4.3.1 Atomic emission spectrometry 292
11.4.3.2 Atomic fluorescence spectrometry 293
11.4.4 Inductively coupled plasma-mass spectrometry 293
11.4.4.1 Ion sources 294
11.4.4.2 Mass analyzers 294
11.4.4.3 Interferences 294
11.4.5 Vapour generation approaches 295
11.4.5.1 Hydride generation 295
11.4.5.2 Mercury vapour generation 296
11.4.6 X-ray fluorescence 297
11.5 Colorimetry and fluorimetry 298
Xii CONTENTS
11.6 Electrochemical methods 299
11.6.1 Anodic stripping voltammetry 299
11.6.2 Ion-selective electrodes 300
11.7 Catalytic methods 301
11.8 Neutron activation analysis 302
11.9 Chromatographic methods 302
11.9.1 Chromatography 302
11.9.2 Speciation 303
11.10 Quality assurance 303
11.11 Summary 304
12 Immunoassays and Enzyme-Based Assays 309
12.1 Introduction 309
12.1.1 Historical development 309
12.2 Basic principles of competitive binding assays 310
12.2.1 Antibody formation 310
12.2.2 Specificity 311
12.2.3 Performing the assay 313
12.2.3.1 Classical radioimmunoassay 313
12.2.3.2 Modern radioimmunoassay (RIA) 315
12.2.4 Non-isotopic immunoassay 315
12.2.5 Assay sensitivity and selectivity 316
12.2.6 Immunoassay development 317
12.2.7 Radioreceptor assays 318
12.3 Heterogeneous immunoassays 318
12.3.1 Tetramefhylbenzidine reporter system 318
12.3.2 Antigen-labelled competitive ELISA 319
12.3.3 Antibody-labelled competitive ELISA 320
12.3.4 Sandwich ELISA 320
12.3.5 Lateral flow competitive ELISA 321
12.3.6 Chemiluminescent immunoassays (CLIA) 321
12.4 Homogenous immunoassays 321
12.4.1 Enzyme-multiplied immunoassay technique (EMIT) 321
12.4.2 Fluorescence polarization immunoassay (FPIA) 323
12.4.3 Cloned enzyme donor immunoassay (CEDIA) 324
12.5 Microparticulate and turbidimetric immunoassays 326
12.5.1 Microparticle enzyme immunoassay (MEIA) 326
12.5.2 Chemiluminescent magnetic immunoassay (CMIA) 327
12.6 Assay calibration, quality control and quality assurance 327
12.6.1 Immunoassay calibration 327
12.6.2 Drug screening 329
12.7 Interferences and assay failures 329
12.7.1 Digoxin 33Q
12.7.1.1 Digoxin-like immunoreactive substances (DLIS) 339
12.7.1.2 Other digoxin-like immunoreactive substances 331
CONTENTS xiii
12.7.1.3 Measurement of plasma digoxin after Fab antibody fragment
administration 331
12.7.2 Insulin and C-peptide 331
12.8 Enzyme-based assays 332
12.8.1 Paracetamol 332
12.8.2 Ethanol 333
12.8.3 Anticholinesterases 334
12.9 Summary 334
13 Toxicology Testing at the Point of Care 339
13.1 Introduction 339
13.1.1 Historical development 340
13.2 UseofPOCT 340
13.2.1 Samples and sample collection 341
13.3 Analytes 343
13.3.1 Ethanol 343
13.3.1.1 Breath ethanol 343
13.3.1.2 Saliva ethanol 343
13.3.2 Drugs of abuse 344
13.3.2.1 Urine testing 345
13.3.2.2 Oral fluid testing 346
13.3.2.3 Sweat testing 346
13.3.3 Paracetamol and salicylates 346
13.3.4 Snake envenomation 347
13.3.5 Therapeutic drug monitoring 347
13.3.5.1 Lithium 348
13.3.5.2 Theophylline 348
13.3.5.3 Anticonvulsants 348
13.4 Interferences and adulterants 348
13.5 Quality assurance 349
13.6 Summary 350
14 Basic Laboratory Operations 353
14.1 Introduction 353
14.1.1 Reagents and standard solutions 354
14.1.2 Reference compounds 354
14.1.3 Preparation and storage of calibration solutions 356
14.2 Aspects of quantitative analysis 358
14.2.1 Analytical error 358
14.2.1.1 Confidence intervals 360
14.2.2 Minimizing random errors 361
14.2.2.1 Preparation of a solution of known concentration 362
14.2.3 Accuracy and Precision 362
14.2.3.1 Assessing precision and accuracy 363
xiv CONTENTS
14.2.3.2 Detecting systematic error (fixed bias) 363
14.2.3.3 Identifying sources of variation: analysis of variance 364
14.2.4 Calibration graphs 365
14.2.4.1 Linear regression 366
14.2.4.2 Testing for linearity 368
14.2.4.3 Weighted linear regression 370
14.2.4.4 Nonlinear calibration curves 370
14.2.4.5 Residuals and standardized residuals 372
14.2.4.6 Blank samples and the intercept 372
14.2.4.7 Method of standard additions 373
14.2.4.8 Limits of detection and quantitation 373
14.2.4.9 Curve fitting and choice of equation 374
14.2.4.10 Single point calibration 375
14.2.5 Batch analyses 375
14.3 Use of internal standards 376
14.3.1 Advantages of internal standardization 378
14.3.1.1 Reproducibility of injection volume 378
14.3.1.2 Instability of the detection system 379
14.3.1.3 Pipetting errors and evaporation of extraction solvent 379
14.3.1.4 Extraction efficiency 380
14.3.1.5 Derivatization and nonstoichiometric reactions 381
14.3.2 Internal standard availability 381
14.3.3 Potential disadvantages of internal standardization 382
14.4 Method comparison 382
14.4.1 Bland-Altman plots 383
14.5 Nonparametric statistics 384
14.5.1 Sign Tests 385
14.5.1.1 Wilcoxon signed rank test 386
14.5.2 Runs test 387
14.5.3 Mann-Whitney £/-test 387
14.5.4 Spearman rank correlation 387
14.5.5 Nonparametric regression 388
14.6 Quality control and proficiency testing 389
14.6.1 Quality control charts 390
14.6.1.1 Shewhart charts 390
14.6.1.2 Cusum charts 390
14.6.1.3 J-chart 39 \
14.6.1.4 Westgard rules 392
14.6.2 External quality assurance 392
14.7 Operational considerations 393
14.7.1 Staff training 393
14.7.2 Recording and reporting results 394
14.7.3 Toxicology EQA schemes 395
14.8 Summary 39-7
CONTENTS xv
15 Absorption, Distribution, Metabolism and Excretion of Xenobiotic
Compounds 399
15.1 Introduction 339
15.1.1 Historical development 399
15.2 Routes of administration 400
15.2.1 Oral dosage 400
15.2.1.1 P-Glycoprotein 402
15.2.1.2 Presystemic metabolism 403
15.2.2 Intravenous injection 403
15.2.3 Intramuscular and subcutaneous injection 404
15.2.4 Sublingual and rectal administration 404
15.2.5 Intranasal administration 405
15.2.6 Transdermal administration 405
15.2.7 Inhalation 405
15.2.8 Other routes of administration 405
15.3 Absorption 406
15.3.1 Passive diffusion 406
15.3.1.1 Partition coefficient 407
15.3.1.2 Ionization 407
15.3.2 Carrier-mediated absorption 408
15.3.3 Absorption from muscle and subcutaneous tissue 409
15.4 Distribution 409
15.4.1 Ion trapping 410
15.4.2 Binding to macromolecules 411
15.4.2.1 Plasma protein binding 411
15.4.3 Distribution in lipid 412
15.4.4 Active transport 412
15.5 Metabolism 412
15.5.1 Phase 1 metabolism 413
15.5.1.1 The cytochrome P450 family 413
15.5.1.2 Other phase 1 oxidases 414
15.5.1.3 Microsomal reductions 416
15.5.1.4 Hydrolysis 416
15.5.2 Phase 2 reactions 417
15.5.2.1 D-Glucuronidation 417
15.5.2.2 O-sulfation and W-acetylation 418
15.5.2.3 O-, N- and S-methylation 419
15.5.2.4 Conjugation with glutathione 419
15.5.2.5 Amino acid conjugation 419
15.5.3 Metabolic reactions of analytical or toxicological importance 420
15.5.3.1 Oxidative dealkylation 420
15.5.3.2 Hydroxylation 421
15.5.3.3 S- and N-oxidation 422
15.5.3.4 Oxidative dehalogenation 423
xvi CONTENTS
15.5.3.5 Desulftiration 425
15.5.3.6 Trans-sulfuration and trans-esterification 425
15.6 Excretion 425
15.6.1 The kidney 426
15.6.1.1 Tubular secretion 427
15.6.1.2 Excretion of metabolites 427
15.6.2 Biliary excretion 427
15.6.2.1 Enterohepatic recirculation 427
15.7 Summary 428
16 Pharmacokinetics 431
16.1 Introduction 431
16.1.1 Historical development 431
16.1.2 Symbols and conventions 432
16.2 Fundamental concepts 432
16.2.1 Rates, rate constants and reaction order 432
16.2.1.1 First-order elimination 433
16.2.1.2 Zero-order elimination 434
16.2.2 Dependence of half-life on volume of distribution
and clearance 434
16.2.2.1 Apparent volume of distribution 435
16.2.2.2 Organ clearance 435
16.2.2.3 Whole body clearance 436
16.3 Absorption and elimination 437
16.3.1 First-order absorption 437
16.3.2 Bioavailability 438
16.3.3 Maximum concentration (Cmax) 439
16.4 Drug accumulation 439
16.4.1 Intravenous infusion 439
16.4.1.1 Loading doses 440
16.4.2 Multiple dosage 440
16.5 Sustained-release preparations 441
16.5.1 Intramuscular depot injection 442
16.5.2 Other sustained-release preparations 443
16.6 Non-linear pharmacokinetics 443
16.6.1 Ethanol 445
16.7 Multicompartment models 447
16.7.1 Calculation of rate constants 449
16.7.2 Volumes of distribution in a two-compartment model 450
16.8 Model-independent pharmacokinetic parameters 451
16.8.1 Apparent volume of distribution 452
16.8.2 Clearance 453
16.8.3 Model-independent approach 453
16.9 Pharmacokinetics and the interpretation of results 454
16.9.1 Back-calculation of dose or time of dose 454
CONTENTS xvii
16.9.1.1 How much substance was administered? 455
16.9.1.2 When was the substance administered? 455
16.9.1.3 Practical examples 455
16.9.1.4 Calculation of time of cannabis exposure 455
16.9.2 Toxicokinetics 458
16.10 Summary 461
17 Clinical Interpretation of Analytical Results 463
17.1 Introduction 463
17.2 Pharmacogenetics 463
17.2.1 Acetylator status 465
17.2.1.1 Isoniazid 465
17.2.1.2 Sulfonamides 465
17.2.2 Cytochrome P450 polymorphisms 466
17.2.2.1 CYP2D6 polymorphism 466
17.2.2.2 CYP2C9 and CYP2C19 polymorphisms 467
17.2.2.3 Other CYP polymorphisms 467
17.2.3 Atypical cholinesterase 467
17.2.4 Glucose-6-phosphate dehydrogenase (G6PD) 468
17.2.5 Alcohol dehydrogenase and aldehyde dehydrogenase 468
17.3 Effects of age, sex and disease on drug disposition 468
17.3.1 Age 468
17.3.1.1 Effect of age on renal function 469
17.3.2 Disease 469
17.3.3 Sex 470
17.4 Enzyme induction and inhibition 471
17.4.1 Enzyme induction 471
17.4.2 Enzyme inhibition 472
17.5 Investigation of acute poisoning 472
17.5.1 Selectivity and reliability of analytical methods 474
17.5.2 Route and duration of exposure and mechanism of toxicity 474
17.5.3 Hair analysis 476
17.5.4 Sources of further information 477
17.6 Postmortem toxicology 478
17.6.1 Choice of sample and sample collection site 479
17.6.2 Assay calibration 480
17.6.3 Interpretation of analytical results 481
17.7 Gazetteer 483
17.7.1 Antidepressants 483
17.7.2 Anti-epileptics and antipsychotics 483
17.7.3 Carbon monoxide and cyanide 483
17.7.4 Cannabis 484
17.7.5 Cardioactive drugs 485
17.7.6 Cocaine 485
17.7.7 Drug-facilitated sexual assault 486
xviii CONTENTS
17.7.8 Ethanol (ethyl alcohol,'alcohol') 487
17.7.9 Heroin/morphine 488
17.7.10 Hypoglycaemic agents 489
17.7.11 Methadone 489
17.7.12 Methylenedioxymetamfetamine and related compounds 490
17.7.13 Volatile substance abuse (VSA) 490
17.8 Summary 490
Index 495 |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| building | Verbundindex |
| bvnumber | BV023324768 |
| callnumber-first | R - Medicine |
| callnumber-label | RA1221 |
| callnumber-raw | RA1221 |
| callnumber-search | RA1221 |
| callnumber-sort | RA 41221 |
| callnumber-subject | RA - Public Medicine |
| classification_rvk | VT 5300 |
| ctrlnum | (OCoLC)123029273 (DE-599)BVBBV023324768 |
| dewey-full | 615.9/07 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 615 - Pharmacology and therapeutics |
| dewey-raw | 615.9/07 |
| dewey-search | 615.9/07 |
| dewey-sort | 3615.9 17 |
| dewey-tens | 610 - Medicine and health |
| discipline | Chemie / Pharmazie Medizin |
| discipline_str_mv | Chemie / Pharmazie Medizin |
| format | Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01987nam a2200493zc 4500</leader><controlfield tag="001">BV023324768</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">00000000000000.0</controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">080602s2007 xxkad|| |||| 00||| eng d</controlfield><datafield tag="010" ind1=" " ind2=" "><subfield code="a">2007013704</subfield></datafield><datafield tag="015" ind1=" " ind2=" "><subfield code="a">GBA753496</subfield><subfield code="2">dnb</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">9780470319345</subfield><subfield code="c">hb : alk. paper</subfield><subfield code="9">978-0-470-31934-5</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">0470319348</subfield><subfield code="c">hb : alk. paper</subfield><subfield code="9">0-470-31934-8</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">9780470319352</subfield><subfield code="c">pbk. : alk. paper</subfield><subfield code="9">978-0-470-31935-2</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">0470319356</subfield><subfield code="c">pbk. : alk. paper</subfield><subfield code="9">0-470-31935-6</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)123029273</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV023324768</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">aacr</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="044" ind1=" " ind2=" "><subfield code="a">xxk</subfield><subfield code="c">GB</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-19</subfield><subfield code="a">DE-Er8</subfield><subfield code="a">DE-20</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RA1221</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">615.9/07</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">VT 5300</subfield><subfield code="0">(DE-625)147745:253</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Fundamentals of analytical toxicology</subfield><subfield code="c">Robert J. Flanagan ... [et al.]</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Chichester, England</subfield><subfield code="b">John Wiley & Sons</subfield><subfield code="c">2007</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">xxxvii, 505 p.</subfield><subfield code="b">Ill., graph. Darst.</subfield><subfield code="c">26 cm</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Includes bibliographical references and index</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Analytical toxicology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Toxicology</subfield><subfield code="x">methods</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Chemistry, Clinical</subfield><subfield code="x">methods</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Specimen Handling</subfield><subfield code="x">methods</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Toxikologische Analyse</subfield><subfield code="0">(DE-588)4078371-6</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">Toxikologische Analyse</subfield><subfield code="0">(DE-588)4078371-6</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Flanagan, Robert J.</subfield><subfield code="e">Sonstige</subfield><subfield code="4">oth</subfield></datafield><datafield tag="856" ind1="4" ind2=" "><subfield code="u">http://www.loc.gov/catdir/toc/ecip0715/2007013704.html</subfield><subfield code="3">Table of contents only</subfield></datafield><datafield tag="856" ind1="4" ind2=" "><subfield code="u">http://www.loc.gov/catdir/enhancements/fy0739/2007013704-d.html</subfield><subfield code="3">Publisher description</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">HBZ Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016508806&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-016508806</subfield></datafield></record></collection> |
| id | DE-604.BV023324768 |
| illustrated | Illustrated |
| index_date | 2024-07-02T20:55:09Z |
| indexdate | 2024-07-09T21:15:54Z |
| institution | BVB |
| isbn | 9780470319345 0470319348 9780470319352 0470319356 |
| language | English |
| lccn | 2007013704 |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-016508806 |
| oclc_num | 123029273 |
| open_access_boolean | |
| owner | DE-19 DE-BY-UBM DE-Er8 DE-20 |
| owner_facet | DE-19 DE-BY-UBM DE-Er8 DE-20 |
| physical | xxxvii, 505 p. Ill., graph. Darst. 26 cm |
| publishDate | 2007 |
| publishDateSearch | 2007 |
| publishDateSort | 2007 |
| publisher | John Wiley & Sons |
| record_format | marc |
| spelling | Fundamentals of analytical toxicology Robert J. Flanagan ... [et al.] Chichester, England John Wiley & Sons 2007 xxxvii, 505 p. Ill., graph. Darst. 26 cm txt rdacontent n rdamedia nc rdacarrier Includes bibliographical references and index Analytical toxicology Toxicology methods Chemistry, Clinical methods Specimen Handling methods Toxikologische Analyse (DE-588)4078371-6 gnd rswk-swf Toxikologische Analyse (DE-588)4078371-6 s DE-604 Flanagan, Robert J. Sonstige oth http://www.loc.gov/catdir/toc/ecip0715/2007013704.html Table of contents only http://www.loc.gov/catdir/enhancements/fy0739/2007013704-d.html Publisher description HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016508806&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Fundamentals of analytical toxicology Analytical toxicology Toxicology methods Chemistry, Clinical methods Specimen Handling methods Toxikologische Analyse (DE-588)4078371-6 gnd |
| subject_GND | (DE-588)4078371-6 |
| title | Fundamentals of analytical toxicology |
| title_auth | Fundamentals of analytical toxicology |
| title_exact_search | Fundamentals of analytical toxicology |
| title_exact_search_txtP | Fundamentals of analytical toxicology |
| title_full | Fundamentals of analytical toxicology Robert J. Flanagan ... [et al.] |
| title_fullStr | Fundamentals of analytical toxicology Robert J. Flanagan ... [et al.] |
| title_full_unstemmed | Fundamentals of analytical toxicology Robert J. Flanagan ... [et al.] |
| title_short | Fundamentals of analytical toxicology |
| title_sort | fundamentals of analytical toxicology |
| topic | Analytical toxicology Toxicology methods Chemistry, Clinical methods Specimen Handling methods Toxikologische Analyse (DE-588)4078371-6 gnd |
| topic_facet | Analytical toxicology Toxicology methods Chemistry, Clinical methods Specimen Handling methods Toxikologische Analyse |
| url | http://www.loc.gov/catdir/toc/ecip0715/2007013704.html http://www.loc.gov/catdir/enhancements/fy0739/2007013704-d.html http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016508806&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT flanaganrobertj fundamentalsofanalyticaltoxicology |