Fundamentals of Analytical Toxicology

545 Pages·2008·4.21 MB·English

by  Robert J. Flanagan

JWBK176-Flanagan-FM JWBK176-Flanagan December21,2007 19:8 CharCount=0
FUNDAMENTALS OF
ANALYTICAL
TOXICOLOGY
RobertJFlanagan
DepartmentofClinicalBiochemistry,
King’sCollegeHospitalNHSFoundationTrust,
London,UK
AndrewTaylor
RoyalSurreyCountyHospital,Guildford,Surrey,UK
IanDWatson
DepartmentofClinicalBiochemistry,UniversityHospitalAintree
Liverpool,UK
RobinWhelpton
SchoolofBiologicalandChemicalSciences,QueenMary,
UniversityofLondon,London,UK
JWBK176-Flanagan-FM JWBK176-Flanagan December21,2007 19:8 CharCount=0
JWBK176-Flanagan-FM JWBK176-Flanagan December21,2007 19:8 CharCount=0
FUNDAMENTALS OF
ANALYTICAL TOXICOLOGY
JWBK176-Flanagan-FM JWBK176-Flanagan December21,2007 19:8 CharCount=0
JWBK176-Flanagan-FM JWBK176-Flanagan December21,2007 19:8 CharCount=0
FUNDAMENTALS OF
ANALYTICAL
TOXICOLOGY
RobertJFlanagan
DepartmentofClinicalBiochemistry,
King’sCollegeHospitalNHSFoundationTrust,
London,UK
AndrewTaylor
RoyalSurreyCountyHospital,Guildford,Surrey,UK
IanDWatson
DepartmentofClinicalBiochemistry,UniversityHospitalAintree
Liverpool,UK
RobinWhelpton
SchoolofBiologicalandChemicalSciences,QueenMary,
UniversityofLondon,London,UK
JWBK176-Flanagan-FM JWBK176-Flanagan December21,2007 19:8 CharCount=0
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Fundamentalsofanalyticaltoxicology/RobertJ.Flanagan...[etal.].
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Includesbibliographicalreferencesandindex.
ISBN978-0-470-31934-5(hb:alk.paper)
ISBN978-0-470-31935-2(pbk.:alk.paper)
1.Analyticaltoxicology. I.Flanagan,RobertJames.
[DNLM:1.Toxicology—methods. 2.Chemistry,Clinical—methods. 3.SpecimenHandling—methods.
QV602F98052007]
RA1221.F862007
615.9(cid:3)07—dc22
2007013704
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Contents
Preface xix
HealthandSafety xxi
Nomenclature,SymbolsandConventions xxiii
AmountConcentrationandMassConcentration xxv
Acknowledgements xxvii
ListofAbbreviations xxix
1 AnalyticalToxicology:Overview 1
1.1 Introduction 1
1.1.1 Historicaldevelopment 1
1.2 Modernanalyticaltoxicology 2
1.2.1 Drugsandpesticides 4
1.2.2 Ethanolandothervolatilesubstances 6
1.2.3 Traceelementsandtoxicmetals 7
1.3 Provisionofanalyticaltoxicologyservices 8
1.3.1 Samplesandsampling 8
1.3.2 Choiceofanalyticalmethod 8
1.3.3 Methodimplementationandvalidation 9
1.3.4 Qualitycontrolandqualityassurance 11
1.4 Applicationsofanalyticaltoxicology 13
1.4.1 Clinicaltoxicology 13
1.4.2 Forensictoxicology 14
1.4.3 Drugabusescreening 15
1.4.4 Therapeuticdrugmonitoring(TDM) 16
1.4.5 Occupationalandenvironmentaltoxicology 17
1.5 Summary 18
2 SampleCollection,Transport,andStorage 21
2.1 Introduction 21
2.2 Clinicalsamplesandsampling 21
2.2.1 Healthandsafety 21
2.2.2 Clinicalsampletypes 23
2.2.2.1 Arterialblood 23
2.2.2.2 Venousblood 23
2.2.2.3 Serum 26
2.2.2.4 Plasma 26
2.2.2.5 Bloodcells 27
2.2.2.6 Urine 28
v
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vi CONTENTS
2.2.2.7 Stomachcontents 28
2.2.2.8 Faeces 28
2.2.2.9 Tissues 29
2.3 Guidelinesforsamplecollectionforanalyticaltoxicology 29
2.3.1 Samplecollectionandpreservation 32
2.3.2 Blood(forquantitativework) 32
2.3.3 Blood(forqualitativeanalysis) 33
2.3.4 Urine 33
2.3.5 Stomachcontents 35
2.3.6 Saliva/oralfluids 36
2.3.6.1 Collectiondevicesforsaliva/oralfluids 37
2.3.7 Sweat 38
2.3.8 Exhaledair 38
2.3.9 Cerebrospinalfluid 38
2.3.10 Vitreoushumour 38
2.3.11 Synovialfluid 39
2.3.12 Liver 39
2.3.13 Othertissues 39
2.3.14 Insectlarvae 39
2.3.15 Keratinaceoustissues(hairandnail) 40
2.3.16 Boneandbonemarrow 41
2.3.17 Injectionsites 41
2.3.18 ‘Sceneresidues’ 41
2.4 Sampletransportandstorage 42
2.5 Commoninterferences 44
2.6 Summary 45
3 SamplePreparation 49
3.1 Introduction 49
3.2 Modesofsamplepreparation 51
3.2.1 Directanalysis/on-linesamplepreparation 51
3.2.2 Proteinpreciptation 52
3.2.3 Microdiffusion 54
3.2.4 Headspaceand‘purge-and-trap’analysis 55
3.2.5 Liquid–liquidextraction 57
3.2.5.1 TheoryofpH-controlledliquid–liquidextraction 63
3.2.5.2 Ion-pairextraction 66
3.2.5.3 Liquid–liquidextractioncolumns 67
3.2.6 Solid-phaseextraction 67
3.2.7 Solid-phasemicroextraction 73
3.2.8 Liquid-phasemicroextraction 76
3.2.9 Supercriticalfluidextraction 77
3.2.10 Acceleratedsolventextraction 78
3.3 Measurementofnonboundplasmaconcentrations 79
3.3.1 Ultrafiltration 80
3.3.2 Equilibriumdialysis 81
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CONTENTS vii
3.4 Hydrolysisofconjugatedmetabolites 82
3.5 Extractionofdrugsfromtissues 84
3.5.1 Hairanalysisfordrugsandorganicpoisons 85
3.6 Derivatization 87
3.7 Summary 88
4 ColourTests,andSpectrophotometricandLuminescenceTechniques 95
4.1 Introduction 95
4.1.1 Historicaldevelopment 95
4.2 Colourtests 96
4.3 UV/visiblespectrophotometry 97
4.3.1 TheBeer–Lambertlaw 98
4.3.2 Instrumentation 100
4.3.2.1 Derivativespectrophotometry 102
4.3.3 Spectrophotometricassays 104
4.3.3.1 Salicylatesinplasmaorurine 106
4.3.3.2 Carboxyhaemoglobin(COHb)inwholeblood 106
4.3.3.3 Cyanideinwholebloodbymicrodiffusion 107
4.3.3.4 Colorimetricmeasurementofsulfonamides 108
4.4 Luminescence 108
4.4.1 Fluorescenceandphosphorescence 108
4.4.1.1 Intensityoffluorescenceandquantumyield 109
4.4.1.2 Instrumentation 110
4.4.1.3 Fluorescenceassays 111
4.4.2 Chemiluminescence 112
4.4.2.1 Instrumentation 114
4.4.2.2 Chemiluminescenceassays 114
4.5 Summary 115
5 IntroductiontoChromatographyandCapillaryElectrophoresis 117
5.1 Generalintroduction 117
5.1.1 Historicaldevelopment 117
5.2 Theoreticalaspectsofchromatography 119
5.2.1 Analytephasedistribution 119
5.2.2 Columnefficiency 121
5.2.3 Zonebroadening 122
5.2.3.1 Multiplepathandeddydiffusion 122
5.2.3.2 Longitudinaldiffusion 123
5.2.3.3 Resistancetomasstransfer 123
5.2.4 Extra-columncontributionstozonebroadening 125
5.2.5 Temperatureprogrammingandgradientelution 125
5.2.6 Selectivity 126
5.2.7 Peakasymmetry 127
5.3 Measurementofanalyteretention 128
5.4 Summary 129
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viii CONTENTS
6 Thin-LayerChromatography 131
6.1 Introduction 131
6.2 Preparationofthin-layerplates 132
6.3 Sampleapplication 133
6.4 Developingthechromatogram 133
6.5 Visualizingthechromatogram 135
6.6 Retentionfactor(Rf) 137
6.7 Toxi-Lab 140
6.8 High-performancethin-layerchromatography 140
6.8.1 Forced-flowplanarchromatography 141
6.9 Quantitativethin-layerchromatography 141
6.10 Summary 142
7 GasChromatography 145
7.1 Introduction 145
7.2 Instrumentation 146
7.2.1 Injectorsandinjectiontechnique 147
7.2.1.1 Cryofocusing/thermaldesorption 148
7.2.2 DetectorsforGC 149
7.2.2.1 Thermal-conductivitydetection 150
7.2.2.2 Flame-ionizationdetection 150
7.2.2.3 Nitrogen–phosphorusdetection 151
7.2.2.4 Electroncapturedetection 152
7.2.2.5 Pulsed-dischargedetection 154
7.2.2.6 Flame-photometricdetection 155
7.2.2.7 Atomic-emissiondetection 155
7.2.2.8 Fourier-transforminfrareddetection 156
7.3 Columnsandcolumnpackings 156
7.3.1 Packedcolumns 157
7.3.2 Capillarycolumns 160
7.3.3 MultidimensionalGC 163
7.4 DerivatizationforGC 164
7.4.1 Electron-capturingderivatives 165
7.5 Chiralseparations 166
7.6 Applicationsofgaschromatographyinanalyticaltoxicology 167
7.6.1 Systematictoxicologicalanalysis 167
7.6.2 Quantitativeanalysisofdrugsandotherpoisons 179
7.6.2.1 Measurementofcarbonmonoxideandcyanide 170
7.6.2.2 Measurementofethanolandothervolatiles 170
7.7 Summary 173
8 High-PerformanceLiquidChromatography 177
8.1 Introduction 177