Dopping

Journal of Chromatography B, 713 (1998) 61–90

Review

Derivatization procedures for gas chromatographic–mass spectrometric determination of xenobiotics in biological samples, with special attention to drugs of abuse and doping agents
a, a b Jordi Segura *, Rosa Ventura , Carmen Jurado
a

´ ` Institut Municipal d’ Investigacio Medica IMIM, Drug Research Unit, Av. Dr. Aiguader 80,08003 Barcelona, Spain b ´ Instituto Nacional de Toxicologıa, P.O. Box 863, 41080 Seville, Spain

Abstract The development of low cost MS detectors in recent years has promoted an important increase in the applicability of GC–MS systems to analyze for the presence of foreign substances in the human body. Drugs and toxic agents are in vivo metabolized in such a way that more polar compounds areusually formed. Derivatization of these metabolites is often an unavoidable requirement for gas chromatographic analysis. Application of derivatization methods in recent years has been relevant, especially for silylation, acylation, alkylation and the formation of cyclic or diastereomeric derivatives. Given the relevance of drug of abuse testing in modern toxicology, main derivatizationprocedures for opiates, cocaine, cannabis, amphetamines, benzodiazepines and LSD have been reviewed. Papers describing the analyses of drugs of abuse in matrixes other than blood, such as hair or sweat, have received especial attention. Advances in derivatization for sports drug testing have been particularly relevant for anabolic steroids, diuretics and corticosteroids. Among the severalmethodologies applied, the formation of trimethylsilyl, perfluoroacyl or methylated derivatives have probed to be both versatile and extensively used. Further advances in derivatization for GC–MS applications in clinical and forensic toxicology will depend on the one hand on the degree of further use of GC–MS for routine applications and, on the other hand, on the alternative progress made fordevelopments in LC–MS or CE–MS. Last but not least, the appearance of comprehensive libraries in which reference spectra for different derivatives of many drugs and their metabolites are collected will have an important impact on the expansion of derivatization in GC–MS for toxicological applications. © 1998 Elsevier Science B.V. All rights reserved. Keywords: Reviews; Xenobiotics; Drugs of abuse;Doping agents

Contents
1. Introduction ............................................................................................................................................................................ 2. Derivatization in GC–MS ........................................................................................................................................................3. Main derivatization methods .................................................................................................................................................... 3.1. Silylation........................................................................................................................................................................ 3.2. Acylation....................................................................................................................................................................... 3.3. Alkylation ...................................................................................................................................................................... 3.4. Formation of cyclic derivatives........................................................................................................................................ *Corresponding author. 0378-4347 / 98 / $19.00 © 1998 Elsevier Science B.V. All rights reserved. PII: S0378-4347( 98 )00089-9 62 63 65 65 66 67 68

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3.5. Chiral...