6c H A P t e r

Analyticaltoxicology

KellIselfeAndsHAyneGAd

IntroductIon

Analytical toxicology is the use of the entire range of qualitative and quantitative chemical, immunochemical, and physical techniques used in sample preparation, separation, assay calibration, detection and identifica-tion, and quantification for the purposes of toxicological research and testing. Examples of the objectives of such analysis include:

l Determining the levels of exposure to potential toxi-cants via air, water, or food.

l Verifying exposure levels to doses for animals in experimental studies.

l Determining levels of xenobiotics and their metabo-lites in animal studies.

l Screening blood and urine for the presence of illicit drugs or their metabolites.

l Screening blood, urine, and tissues for the presence of toxic drugs, agents, or their metabolites.

l Measuring levels of endogenous compounds and molecules to evaluate organ function and damage (clinical chemistry).

l Identifying metabolites and macromolecular adjuncts to identify mechanisms of action.

The diagnosis and treatment of health problems induced by chemical substances and the closely allied field of therapeutic drug monitoring rely on analytic toxicology. Advances in analytic toxicology have added both power and problems to toxicology, with the increases in sensitivity and specificity. Although the analytes are present in matrices identical or simi-lar to those seen in forensic toxicology, the results must be reported rapidly to be of use to clinicians in

treating patients. The requirement of a rapid turna-round time limits the number of chemicals that can be measured because methods, equipment, and person-nel must all be available for an instant response to toxicological emergencies. Investigations for an ‘unknown’ drug or poison are usually carried out on specimens of urine, blood, or specific tissues.

relatedtopic

Forensic toxicology.

resources

Books

Baselt RC (2004)The Disposition of Toxic Drugs and Chemicals in ManFoster City, CA: Chemical Toxicology Institute.

A single source providing an extensive compilation on the disposition of over 640 drugs and chemicals most frequently encountered in episodes of human poison-ing. The data relate to the body fluid concentrations of substances in normal or therapeutic situations, concen-trations in fluids and tissues in instances of toxicity and the known metabolic fate of these substances in man. Each drug/chemical is broken down into: Occurrence and Usage; Blood Concentrations; Metabolism and Excretion; Toxicity; and Analysis. This 7th edition has been expanded with an additional 139 drugs or chemi-cals including a number of animal toxins, antibiotics, antidepressants, antidiabetics, antifungal agents, anti-hyperlipidemic drugs, antineoplastic drugs, antiseptics,

67

INFORMATION RESOURCES IN TOXICOLOGY, FOURTH EDITION

Copyright © 2009 by Academic Press.

All rights of reproduction in any form reserved.

Resources68

antiviral agents, diuretics, herbal medicines, herbicides, laxatives, solvents, sedative-hypnotics, pesticides, and drugs used to treat Alzheimer’s disease.

Botsoglou NA, Fletouris DJ (2001)Drug Residues in FoodsNew York: Marcel Dekker, Inc.

A volume in the Food Science and Technology series which focuses on veterinary drug residues in food products, their toxicity and analysis.

Bradenberger H, Maes RAA (ed.) (1997)Analytical Toxicology for Clinical, Forensic and

Pharmaceutical Chemists (Clinical Biochemistry)Berlin, Germany: Walter de Gruyter & Co.

This book will be of use to clinical and forensic toxi-cologists as well as to pharmacists involved in analyti-cal work. The critical evaluations of the analytical possibilities may help with the choice of methods, the additional information with the determination of the goals of an investigation and the interpretation of its results. In addition to all the analytical and toxicologi-cal information the book contains, it also tries to teach the analytical toxicologist to place his technical obliga-tions into a larger context.

Flanagan RJ (2005)Developing Analytical Toxicology Services: Principles

and GuidanceGeneva, Switzerland: WHO/ILO/UNEP.

Flanagan RJ, Braithwaite RA, Brown SS, Widdop B, Wolff FA (eds.) (1995)

Basic Analytical ToxicologyGeneva, Switzerland: World Health Organization.

The aim of this manual is to help hospital laboratories in developing countries to provide a basic analytical toxicology service using a minimum of special appa-ratus. It is not intended to replace standard texts, but to provide practical information on the analysis of a number of substances frequently involved in acute poisoning incidents. Common pitfalls and problems are emphasized throughout, and basic health and safety precautions for laboratory workers are also discussed.

Gad SC, Wexler P, Anderson BD, et al (eds.) (2005)Analytical toxicology. In: Encyclopedia of Toxicology

pp. 113–116.Oxford, UK: Elsevier Inc.

Overview of the definition of analytical toxicology as well as analysis of common toxic substances and analytical techniques.

Gupta SK, Singh U, Velpandian T (eds.) (2002)Analytical Toxicology for Poisoning Management and

ToxicovigilanceNew Dehli, India: Narosa Publishing House.

This text covers services of the analytical toxicology laboratory, from common general emergency medicine to specialized treatment units. It defines procedures for critical quantitative analysis in treating acute poisoning cases and is a useful reference for those in poisoning diagnosis, case management, and prevention.

Sue Jickells, Adam Negrusz (eds.) (2008)Clarke’s Analytical ToxicologyLondon: Pharmaceutical Press.

Mieczkowski T (ed.) (1999)Drug Testing Technology: Assessment of Field

Applications (Methods in Analytical Toxicology)Boca Raton, FL: CRC Press.

This book covers a wide range of research currently being done in drug analysis, Drug Testing Technology: Assessment of Field Applications compares and evaluates various methods used to determine abused drugs taken by individuals. Chapters provide overviews of drug incorporation into hair; the use of hair analysis for compliance measurement in the use of anti-epilep-tic medications; and the application of drug testing to the psychiatric treatment of substance abuse disorders.

Moffat AC, Osselton MD, Widdop B (2004)Clarke’s Analysis of Drugs and Poisons, 3rd editionLondon: Pharmaceutical Press.

This is a two-volume reference set previously known as Clarke’s Isolation and Identification of Drugs, this prac-tical manual and standard reference work provides the definitive source of analytical data for drugs and poisons. It is intended for use primarily by scientists faced with identifying and quantifying these sub-stances in body fluids, tissue samples, and pharma-ceutical and industrial products. Volume 1 includes 31 chapters covering all practice areas and analytical pro-cedures in analytical toxicology as well as applications of analytical toxicology techniques, Volume 2 includes 1730 drug monographs.

NIOSH Manual of Analytical Methods, 4th edition (NIOSJ Manual of Analytical Methods), (1994)

Web: http://www.cdc.gov/niosh/nmam/

Satinder A, Scypinski S (2001)Handbook of Modern Pharmaceutical AnalysisSan Diego, CA: Academic Press.

A modern text on methodology for the analysis of pharmaceutical active ingredients and formulations.

6. Analytical Toxicology 69

Wong Steven HY, Irving Sunshine (eds.) (1997)Handbook of Analytical Therapeutic Drug Monitoring

and ToxicologyBoca Raton, FL: CRC Press.

This volume facilitates searches for appropriate tech-niques, describes recent contributions from leading investigators, and provides valuable evaluations and advice. Discover how to use non-invasively obtained specimens to your best advantage. The text features alternative biological specimens such as hair, meco-nium, saliva, sweat, and vitreous humor, which are not extensively used because they require more sensi-tive procedures than other biological specimens. How to overcome these limitations is a major topic of the handbook. Experts describe basic principles of inno-vative techniques and detail how they can be adapted to analyzing alternative biological specimens. The evaluations of the pros and cons of various advances in immunodiagnostics and how they apply to analytes will help you determine their suitability to your own laboratory. The Handbook of Analytical Therapeutic Drug Monitoring and Toxicology helps you make the most of innovative procedures that will open the doors to pro-ductive laboratory practices.

Venn RF (2000)Principles and Practice of BioanalysisPhiladelphia, PA: Taylor and Francis.

A modern text on methodology for the analysis of active pharmaceutical ingredients and their metabo-lites in biological matrices.

reviewArticles

Baars AJ (1996) Analytical toxicology: From environ-mental monitoring to residue analysis. Arh. Hig. Rada. Toksikol. 47(2): 199–209.

Bost RO (1993) Hair analysis – Perspectives and limits of a proposed forensic method of proof: A review. Forensic Sci. Int. 63: 31–42.

De Zeeuw RA (1998) Recent developments in analyti-cal toxicology: for better or for worse. Toxicol. Lett. 102–103: 103–108.

De Zeeuw RA (2004) Substance identification: the weak link in analytical toxicology. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 811(1): 3–12.

Dewan A, Pandva CB, Saiyed HN (1998) Basic analyti-cal toxicology. Indian J. Med. Res. 107: 109–110.

El-Masri HA, Reardon KF, Yang RSH, et al (1997) Integrated approaches for the analysis of toxicologic interactions of chemical mixtures. Crit. Rev. Toxicol. 27(2): 175–197.

Ferrara DS, Tedeschi L, Frison G, Brusini G (1998) Quality control in toxicological analysis. J. Chromatogr. B. Biomed. Sci. 713: 227–243.

Flanagan RJ (1995) The poisoned patient: The role of the laboratory. Br. J. Biomed. Sci. 52: 202–213.

Flanagan RJ (1998) Guidelines for the interpretation of analytical toxicology results and unit of measure-ment conversion factors. Ann. Clin. Biochem. 35(Pt.2): 261–267.

Flanagan RJ, Widdop B, Ramsey JD, Loveland M (1988) Analytical toxicology. Hum. Toxicol. 7(5): 489–502.

Flanagan RJ, Connally G (2005) Interpretation of ana-lytical toxicology results in life and at postmortem. Toxicol Rev. 24(1): 51–62.

Flanagan RJ, Connally G, Evans JM (2005) Analytical toxicology: guidelines for sample collection post-mortem. Toxicol. Rev. 24(1): 63–71.

Flanagan RJ, Morgan PE, Spencer EP, Whelpton R (2006) Micro-extraction techniques in analytical toxicology: short review. Biomed. Chromatogr. 20(6): 530–538.

Hoja H, Marquet P, Verneuil B, et al (1997) Applications of liquid chromatography-mass spec-trometry in analytical toxicology. A review. J. Anal. Toxicol. 21(2): 116–126.

Kraemer T, Paul LD (2007) Bioanalytical procedures for determination of drugs of abuse in blood. Anal. Bioanal. Chem. 338: 1415–1435.

Maurer Hans H (2005) Advances in analytical toxicol-ogy: The current role of liquid chromatography mass spectrometry in drug quantification in blood and oral fluid. Anal. Bioanal. Chem. 381(1): 110–118.

Maurer HH (2007) Analytical toxicology. Anal. Bioanal. Chem. [Epub ahead of print].

Pragst F (2007) Application of solid-phase micro-extraction in analytical toxicology. Anal. Bioanal. Chem. 338: 1311.

Smith ML, Vorce SP, Holler JM, et al (2007) REVIEW: Modern instrumental methods in forensic toxicol-ogy. J. Anal. Toxicol. 31(50): 237–253.

Tracqui A, Kintz P, Mangin P (1995) Systemic toxico-logical analysis using HPLC/DAD. J. Forensic Sci. 40(2): 254–262.

Van Bocxlaer JF (2005) Recent trends in analytical pro-cedures in forensic toxicology. Ther. Drug Monit. 27(6): 752–755.

Van Emon JM, Gerlach CL, Bowman K (1998) Bioseparation and bioanalytical techniques in environmental monitoring. J. Chromatogr. B. Biomed. Appl. 715(1): 211–228.

Resources70

Willie SM, Lambert WE (2007) Recent developments in extraction procedures relevant to analytical toxi-cology. Anal. Bioanal. Chem. 338: 1381–1391.

Journals

Analytical and Bioanalytical ChemistryAnnals of Clinical BiochemistryBiomedical ChromatographyForensic Science InternationalJournal of Analytical ToxicologyJournal of Chromatography B (formerly known as Journal of Chromatography B: Biomedical Sciences and Applications)Journal of Forensic ScienceTherapeutic Drug Monitoring

Website

World Health Organization (WHO) Analytical Toxicology: http://www.who.int/ipcs/publications/training_poisons/basic_analytical_tox/en/index.html

database

The NIOSH Manual of Analytical Methods (NMAM®)

The NIOSH Manual of Analytical Methods database is a compilation of methods for sampling and analysis of contaminants in workplace air, and in the bodily fluids of workers who are occupationally exposed to that air. These methods have been developed specifi-cally to have adequate sensitivity to detect the lowest concentrations and sufficient flexibility of range to detect concentrations exceeding safe levels of expo-sure, as regulated by OSHA and recommended by NIOSH. The Threshold Values (TLV™) and Biological Exposure Indices (BEI™) of the American Conference of Governmental Industrial Hygienists (ACGIH) are also cited.