Hair Analysis in Clinical and Forensic Toxicology

 
 
Academic Press
  • 1. Auflage
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  • erschienen am 25. Juni 2015
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  • 392 Seiten
 
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978-0-12-801710-4 (ISBN)
 

Hair Analysis in Clinical and Forensic Toxicology is an essential reference for toxicologists working with, and researching, hair analysis. The text presents a review of the most up-to-date analytical methods in toxicological hair analysis, along with state-of-the-art developments in the areas of hair physiology, sampling, and pre-treatments, as well as discussions of fundamental issues, applications, and results interpretation.

Topics addressed include the diagnosis of chronic excessive alcohol drinking by means of ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE), the early detection of new psychoactive substances, including designer drugs, the development of novel approaches to screening tests based on mass spectrometry, and the detection of prenatal exposure to psychoactive substances from the analysis of newborn hair.


  • Unites an international team of leading experts to provide an update on the cutting-edge advances in the toxicological analysis of hair
  • Demonstrates toxicological techniques relating to a variety of scenarios and exposure types
  • Ideal resource for the further study of the psychoactive substances, drug-facilitated crimes, ecotoxicology, analytical toxicology, occupational toxicology, toxicity testing, and forensic toxicology
  • Includes detailed instructions for the collection, preparation, and handling of hair, and how to best interpret results


Docteur en pharmacie, docteur en toxicologie
  • Englisch
  • USA
Elsevier Science
  • 8,90 MB
978-0-12-801710-4 (9780128017104)
0128017104 (0128017104)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Hair Analysis in Clinical and Forensic Toxicology
  • Copyright Page
  • Contents
  • Foreword
  • List of Contributors
  • 1 Anatomy and Physiology of Hair, and Principles for its Collection
  • 1.1 Introduction
  • 1.2 Hair Anatomy and Physiology
  • 1.3 Classification of Hair Types
  • 1.4 Hair Growth Rates
  • 1.5 Hair Color
  • 1.6 Mechanisms of Drug Incorporation
  • 1.7 Incorporation from the Bloodstream, Sebum and Sweat
  • 1.8 Incorporation from External Contamination
  • 1.9 Dose-Response Relationship
  • 1.10 Melanin Binding
  • 1.11 Sample Collection Protocols
  • 1.12 Collection Procedure
  • 1.12.1 Workplace Drug Testing
  • 1.12.2 Drug-Facilitated Crime
  • 1.12.3 Postmortem Investigations
  • 1.13 Discussion
  • 1.14 Conclusion
  • References
  • 2 Hair Sample Preparation, Extraction, and Screening Procedures for Drugs of Abuse and Pharmaceuticals
  • 2.1 Introduction
  • 2.2 Sample Preparation
  • 2.2.1 Segmentation
  • 2.2.2 Washing
  • 2.2.3 Obtaining a Representative Sample Aliquot
  • 2.3 Analyte Extraction
  • 2.3.1 Hydrolysis of the Hair Matrix
  • 2.3.2 Solvent Incubation
  • 2.4 Screening Strategies
  • 2.4.1 Immunoassays
  • 2.4.2 Chromatographic Procedures
  • 2.5 Concluding Remarks
  • References
  • 3 External Contamination: Still a Debate?
  • 3.1 Introduction
  • 3.1.1 Incorporation from the Bloodstream
  • 3.1.2 Incorporation from Sweat and Other Secretions
  • 3.1.3 Incorporation from External Contamination
  • 3.2 External Contamination: Commonly Encountered Drugs
  • 3.2.1 Smoke and Passive Inhalation
  • 3.2.2 Surface/Environmental Contamination: Poor Housekeeping
  • 3.3 Alcohol: FAEE and EtG
  • 3.4 Concluding Remarks
  • References
  • 4 Alcohol Biomarkers in Hair
  • 4.1 Introduction
  • 4.2 Alcohol Amount, Drinking Pattern, and Minor Metabolites of Ethanol in Hair
  • 4.3 Ethyl Glucuronide
  • 4.3.1 Formation and Incorporation of EtG in Hair
  • 4.3.2 Analytical Determination of EtG in Hair
  • 4.3.2.1 Sampling, Segmentation, and Storage
  • 4.3.2.2 External Decontamination
  • 4.3.2.3 Grinding or Cutting to Small Pieces
  • 4.3.2.4 Hair Extraction
  • 4.3.2.5 Clean-up
  • 4.3.2.6 GC-MS and GC-MS/MS Procedures
  • 4.3.2.7 LC-MS/MS Procedures
  • 4.3.2.8 Validation and Quality Assurance
  • 4.3.3 Alcohol Consumption and EtG Concentrations in Hair
  • 4.3.3.1 Animal Experiments
  • 4.3.3.2 Meta-analysis of EtG Concentration in Human Hair
  • 4.3.3.3 Basic EtG Levels in Hair of Abstainers
  • 4.3.3.4 EtG in Hair after Single Excessive Drinking
  • 4.3.3.5 Prospective Studies
  • 4.3.3.6 EtG in Hair and Retrospectively Self-Reported Drinking Data
  • 4.3.3.7 Effect of Decreased Kidney Function
  • 4.3.4 Cutoff Values, Sensitivity, and Specificity
  • 4.3.5 EtG in Nonhead Hair
  • 4.3.5.1 General Differences as Compared to Scalp Hair
  • 4.3.5.2 EtG in Pubic Hair
  • 4.3.5.3 EtG in Axillary Hair
  • 4.3.5.4 EtG in Chest, Arm, and Leg Hair
  • 4.3.6 Effect of Hair Color, Hair Care, and Cosmetic Treatment
  • 4.3.7 Effect of Other Parameters and Habits on EtG in Hair
  • 4.4 Fatty Acid Ethyl Esters
  • 4.4.1 Formation and Incorporation of FAEEs in Hair
  • 4.4.2 Analytical Determination of FAEEs in Hair by HS-SPME and GC-MS
  • 4.4.2.1 Sample Pretreatment and External Decontamination
  • 4.4.2.2 Hair Extraction
  • 4.4.2.3 Headspace Solid-Phase Microextraction
  • 4.4.2.4 Gas Chromatography-Mass Spectrometry
  • 4.4.2.5 Calibration and Validation
  • 4.4.2.6 Attempts for Improvement and Alternative Methods
  • 4.4.3 FAEE Concentrations in Hair and Alcohol Consumption
  • 4.4.3.1 Concentration Ratio of the Four FAEEs
  • 4.4.3.2 FAEE Concentrations in Hair and Self-Reported Drinking Data
  • 4.4.3.3 FAEEs in Postmortem Hair Samples
  • 4.4.4 Cutoff Values, Sensitivity, and Specificity
  • 4.4.5 Effect of Hair Color, Hair Care, and Cosmetic Treatment
  • 4.4.6 FAEEs in Nonhead Hair
  • 4.4.7 Other Parameters with Effect on FAEE Concentration in Hair
  • 4.5 Combined Use of EtG and FAEEs
  • 4.5.1 EtG and FAEEs in Abstinence Assessment
  • 4.5.2 EtG and FAEE for Detection of Chronic Alcohol Abuse
  • 4.5.3 Combined Interpretation of EtG and FAEE in Hair
  • 4.5.4 Time Period Between Initiation of Abstinence and Collection of Hair Sample
  • 4.6 Comparison of EtG and FAEE in Hair with Other Alcohol Markers
  • 4.7 Practical Applications of EtG and FAEE in Hair
  • 4.7.1 Driving Ability Examination and Driver's License Regranting
  • 4.7.2 Workplace and Preemployment Alcohol Testing
  • 4.7.3 Prenatal Alcohol Exposure
  • 4.7.4 Family Courts and Child Custody Cases
  • 4.7.5 Liver Transplantation and Patients with Liver Disease
  • 4.7.6 Postmortem Cases and Historical Study
  • 4.8 Cocaethylene
  • 4.9 Outlook
  • References
  • 5 Clinical Applications of Hair Analysis
  • 5.1 Introduction
  • 5.2 Hair Analysis in Maternal, Neonatal, and Child Health
  • 5.2.1 Fetal Alcohol Spectrum Disorder
  • 5.2.2 Neonatal Abstinence Syndrome
  • 5.2.3 Measuring Drugs of Abuse in Neonatal Hair
  • 5.2.3.1 Physiology
  • 5.2.3.2 Dose-Response
  • 5.2.3.3 Extraction
  • 5.2.4 Social Pediatric Risks
  • 5.2.4.1 Neonatal Considerations
  • 5.2.4.2 Pediatric Hair Analysis and Passive Exposure Assessment
  • 5.3 Clinical Applications of Hair Cortisol Analysis
  • 5.3.1 Measuring Chronic Stress
  • 5.3.2 Stress and Acute Myocardial Infarction
  • 5.3.3 Analysis of Cortisol in Hair
  • 5.4 Future Clinical Applications of Hair Testing
  • References
  • 6 Experiences in Child Hair Analysis
  • 6.1 Introduction
  • 6.2 Age as a Factor of Influence of Drug Distribution
  • 6.3 Differences in Children's Hair versus Adults
  • 6.4 Case Reports
  • 6.5 Conclusion and Perspectives
  • References
  • 7 Hair Analysis for the Biomonitoring of Human Exposure to Organic Pollutants
  • 7.1 Introduction
  • 7.1.1 A Recently Investigated Field
  • 7.1.2 From Feasibility to Field Studies
  • 7.2 The Challenge of Assessing Environmental Exposure
  • 7.2.1 Facing Low Concentration Levels
  • 7.2.2 Is the Method Sensitive Enough?
  • 7.2.3 Sensitivity and Rate Positive Detection
  • 7.3 Sample Pretreatment
  • 7.3.1 Decontamination Procedures
  • 7.3.2 Artificial Contamination
  • 7.3.3 The Specificity of OPs
  • References
  • 8 Workplace Drug Testing
  • 8.1 Introduction
  • 8.2 Ideal Matrix in the Workplace Scenario
  • 8.2.1 Preemployment
  • 8.2.2 Random
  • 8.2.3 Postaccident or Incident
  • 8.2.4 Return to Work
  • 8.3 Evidence that a Hair Drug Test Detects More Users than Urine
  • 8.4 Procedures for Drug Testing Using Hair
  • 8.4.1 Collection
  • 8.4.2 Growth Rate
  • 8.4.3 Body Hair
  • 8.4.4 Window of Detection
  • 8.4.5 Why Hair Decontamination and Analysis of the Wash Residue?
  • 8.4.6 Extraction
  • 8.4.7 Immunochemical Screens
  • 8.4.8 Confirmations
  • 8.5 Accreditation
  • 8.6 Interpretation and Reporting
  • 8.6.1 Can We Tell the Amount of Drug Used?
  • 8.6.2 Can We Compare Results Between Individuals?
  • 8.6.3 It Is Possible to Grade the Amount of Drug Used Within the Same Individual
  • 8.6.4 It Is Possible to Compare the Results with Data Accumulated by the Laboratory
  • 8.6.5 Can We Tell the Frequency of Drug Use?
  • 8.6.6 Effect of Hair Cosmetics
  • 8.6.7 Hair Color
  • 8.6.8 Cutoffs: How Drug Test Results Are Interpreted to Clients
  • 8.7 Hair Analysis in the Workplace
  • 8.7.1 Hair Analysis Data for Preemployment in Brazil
  • 8.7.2 Data from a Preemployment Setting in the United Kingdom, Brazil, and Australia
  • 8.8 Conclusions
  • References
  • 9 Forensic Applications of Hair Analysis
  • 9.1 Introduction
  • 9.2 Advantages of Hair Analysis
  • 9.3 Limitations of Hair Analysis
  • 9.4 Applications of Hair Analysis in Forensic Toxicology
  • 9.4.1 Postmortem Toxicology
  • 9.4.1.1 Putrefied and Mummified Cadavers
  • 9.4.1.2 Loss of Tolerance
  • 9.4.1.3 Multiorgan Damage Caused by Long-Term Consumption
  • 9.4.1.4 Pitfalls in Hair Analysis in Postmortem Toxicology: External Contamination with Biological Fluids
  • 9.4.2 Drug-Facilitated Crimes
  • 9.4.2.1 Substances Used
  • 9.4.2.2 Analytical Strategies
  • 9.4.2.3 Drug-Facilitated Sexual Assaults
  • 9.4.2.4 DFC in the Elder People
  • 9.4.2.5 DFC in Children
  • 9.4.2.6 Pitfalls in Hair Analysis in DFCs: Sequential Hair Analysis
  • 9.4.3 Divorce and Child Custody Proceedings
  • 9.4.3.1 Hair versus Urine to Estimate Drug Abuse
  • 9.4.4 Follow-Up of Detoxification Programs
  • 9.4.4.1 Window of Detection in Hair Samples
  • References
  • 10 Doping, Applications of Hair Analysis
  • 10.1 Introduction
  • 10.2 Hair Testing for Positive Identification of Prohibited Substances
  • 10.2.1 S0: Nonapproved Substances
  • 10.2.2 S1.1.a: Synthetic Anabolic Androgenic Steroids
  • 10.2.3 S1.1.b: Endogenous AASs
  • 10.2.4 S1.2: Other Anabolic Agents
  • 10.2.5 S3: Beta-2 Agonists
  • 10.2.6 S4: Hormone and Metabolic Modulators
  • 10.3 Hair Testing as Additional Evidence in Presumptive Doping Cases
  • 10.3.1 Case 1: Clenbuterol
  • 10.3.2 Case 2: MDMA
  • 10.4 Hair Testing for Doping Control in Animals
  • References
  • 11 Detection of New Psychoactive Substances
  • 11.1 Introduction
  • 11.2 The Challenge of NPS Detection
  • 11.3 Ketamine
  • 11.3.1 Analysis of Real Samples
  • 11.3.1.1 Case Study 1
  • 11.3.1.2 Case Study 2
  • 11.3.1.3 Case Study 3
  • 11.3.1.4 Case Study 4
  • 11.3.1.5 Case Study 5
  • 11.3.1.6 Case Study 6
  • 11.3.1.7 Case Study 7
  • 11.3.1.8 Case Study 8
  • 11.3.1.9 Case Study 9
  • 11.3.1.10 Case Study 10
  • 11.3.1.11 Case Study 11
  • 11.3.1.12 Case Study 12
  • 11.3.1.13 Case Study 13
  • 11.3.1.14 Case Study 14
  • 11.3.2 Discussion
  • 11.4 Synthetic Cathinones
  • 11.4.1 GC-MS Methods
  • 11.4.2 LC-MS/MS Methods
  • 11.5 Synthetic Cannabinoids
  • 11.5.1 Detection of Metabolites
  • 11.6 Conclusions
  • Acknowledgments
  • References
  • 12 New Challenges and Perspectives in Hair Analysis
  • 12.1 Introduction
  • 12.2 Conditioning Factors and Sources of Variability
  • 12.2.1 Physical and Chemical Agents
  • 12.2.2 Interaction Between Hair Constituents and Incorporated Substances
  • 12.2.3 Distribution of the Xenobiotic Substances Within the Hair
  • 12.2.4 Individual Factors
  • 12.3 Innovative Technologies and Instrumental Advancements
  • 12.3.1 Broad-Spectrum Toxicological Analysis
  • 12.3.2 Highly Demanding Investigations
  • 12.3.3 Minute Hair Availability and Single Hair Analysis
  • References
  • Index
Chapter 2

Hair Sample Preparation, Extraction, and Screening Procedures for Drugs of Abuse and Pharmaceuticals


Robert Kronstrand1,2, Malin Forsman1 and Tor Seldén1,2,    1National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden,    2Division of Drug Research, Linköping University, Linköping, Sweden

The aims of this chapter are to give the reader a good insight into the practical preanalytical aspects of hair testing and also to inform about the different screening strategies that can be used. The chain of events leading up to the accurate interpretation of results starts already at the sampling site but this chapter will focus on the preparation of hair samples, performed at the laboratory, to ensure a valid result. This includes segmentation, homogenization, and the extraction of drugs from the hair matrix. After extraction, screening of drugs and medications is usually performed and if presumptive positive a confirmatory analysis is performed. Common strategies include immunoassays that are quick, sensitive, and cost-effective. However, chromatographic techniques are used more and more particularly by forensic laboratories where the positivity rate is much higher.

Keywords


Hair; segmentation; extraction; screening; immunoassay; chromatography

2.1 Introduction


The aims of this chapter are to give the reader a good insight into the practical preanalytical aspects of hair testing and also to inform about the different screening strategies that can be used. The chain of events leading up to the accurate interpretation of results starts already at the sampling site but this chapter will focus on the preparation of hair samples, performed at the laboratory, to ensure a valid result. This includes segmentation, homogenization, and the extraction of drugs from the hair matrix. After extraction, screening of drugs and medications is usually performed and if presumptive positive a confirmatory analysis is performed. Depending on the problem trying to be solved, the strategies for screening will vary. Common strategies include immunoassays that are quick, sensitive, and cost-effective, especially when the proportion of positive samples is low. However, chromatographic techniques are used more and more particularly by forensic laboratories where the positivity rate is much higher. Sometimes, the chromatographic screening methods are used as the end point even though, in contrast to forensic best practice, only one analysis has been performed. The reason is the high power of identification of specific analytes as well as accurate determination of their concentration that can be retrieved from such methods in combination with an increased security of sample integrity using barcodes and scanners throughout the laboratory. Also, the use of time-of-flight mass spectrometric methodology enables the analytical toxicologist to further explore many analytes in the same run even though true untargeted screening methods are rare. However, the analytical work begins with obtaining an appropriate and representative aliquot of the hair to be used for extraction and analysis.

2.2 Sample Preparation


2.2.1 Segmentation


Even though analysis may be performed on the whole hair, it is very common to use one or more segments of the sample. A commonly used segment length is the 3-cm proximal portion representing hair grown during the last 3 months. However, depending on the case, different strategies for segmentation may apply. Several short segments can provide a much more detailed profile of an individual's drug exposure than a single segment. The accuracy of such segmental analysis depends on both the sampling and the segmentation procedure at the laboratory. Poor sampling procedures with unparallel hair strands may severely lower the segmental resolution.

When given a single dose of a drug or medication one would assume that only one segment of hair, grown at the time after administration, would be positive. However, even under controlled study conditions the drug may be found in more than one segment [1]. This is illustrated in Figure 2.1 depicting data from a study with single intake of flunitrazepam. The subject received a single 2 mg dose of flunitrazepam and hair samples were obtained after 2 and 4 months. The samples were segmented in 5 mm segments and analyzed with liquid chromatography tandem mass spectrometry (LC-MS/MS). In the 2-month sample the concentration of the metabolite, 7-aminoflunitrazepam, is high in S3 corresponding to the time of intake whereas the surrounding segments have much less drug. In the 4-month sample, segment S7 should represent the time of intake but both segments S7 and S8 have similar concentrations, significantly lower than those in the previous sample. This illustrates how the results are obscured over time when hair from different growth cycles is included in the measurement or if hair has shifted during sampling, transport, and segmentation. It is important to understand that when investigating a single intake, the use of large segments will dilute the incorporated drug and cause false negative results. Figure 2.2 illustrates in a schematic way, how the resolution in time is increasing with shorter segments and also that the measured concentrations increases because of less dilution from drug-free hair. The Society of Hair Testing (SoHT) recommends that only hair cut from the scalp with the root end identified should be subjected to segmental analysis. One should also be aware of the possibility that the hair is not cut right at the scalp, as recommended. Indeed, LeBeau et al. showed this in a study where they instructed experienced and unexperienced samplers to obtain hair samples [2]. The mean length of hair remaining on the scalp was 0.8 cm. Therefore, one should be careful when extrapolating the hair length used to a particular time period using the sampling date as baseline.


Figure 2.1 Segmental outcome of hair samples obtained from a subject approximately 2 and 4 months after a single intake of 2 mg flunitrazepam using 5 mm segments for analysis. Segments S3 and S7 correspond to the time of intake.
Figure 2.2 Schematic results from analysis of different segment lengths of a given hair sample; upper panel 0.5-cm segment, middle panel 1-cm segment, and lower panel 3-cm segment. Shorter segments provide not only higher resolution but also higher concentrations in the segment corresponding to the time of intake because the dilution with negative hair is less than in a longer segment.

Segmental hair analysis can also provide detailed temporal information about medication intake or drug abuse pattern. If the purpose is to evaluate the possible tolerance or nontolerance to certain drugs or groups of drugs, the more recent hair segments are most relevant to analyze. For opioid drugs, tolerance develops gradually, as does the loss of tolerance. The time frame for these processes are poorly understood, and complicated by the fact that tolerance to the euphoric effects may be different from that to respiratory depression. A period of abstinence of 7-14 days is however likely to result in a marked reduction in tolerance to opioid drugs, implying that hair segments should be rather short to capture this time period accurately. Positive detections in hair segments of 1 cm or longer may not discriminate between intakes that occurred during a few days before the demise from exposure about 4 weeks back. Segmentation into 5 mm long segments seems to be relevant in opioid overdose cases to separate cases with a recent abstinence from cases with continuous use [3]. To accurately follow the distribution of drugs in the hair over time washing is important. The washing steps should be performed after the segmentation to avoid contamination along the hair shaft during the washing process.

2.2.2 Washing


Since hair is growing on the body surface there is a risk of contamination from outer sources. (This is described in Chapter 3 of this book.) Washing of the hair before analysis is therefore an important step. The washing has two main purposes: first, to remove hair care products, sweat, sebum, or surface material that may interfere with the analysis or that may reduce extraction recovery and second, to remove potential external contamination of drugs from the environment. However, there are probably as many washing procedures as there are laboratories and the debate about the correct way to perform and interpret washing results is still ongoing. The SoHT recommends that laboratories should have a procedure for washing hair samples prior to analysis, that the procedure should include washing steps with both organic solvent and aqueous solutions, and that the laboratory should investigate to what extent their wash procedure removes surface contamination [4].

The use of a first step with an organic solvent that does not swell the hair or penetrate the inner structure of hair will remove hair care products and surface contamination only whereas aqueous solutions also will extract drugs from the hair matrix. Today, it is accepted that drugs deposited into hair are from several sources including the blood stream, sweat, sebum, and other secretions. This means that a drug user or patient, in addition to incorporating drugs through the bloodstream also exposes the hair to an "internal external" contamination that can be very difficult to differentiate from...

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