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Scarth J.P.,A Quotient Bioresearch Ltd Company | Teale P.,A Quotient Bioresearch Ltd Company | Kuuranne T.,United Medix Laboratories Ltd
Drug Testing and Analysis | Year: 2011

A detailed understanding of equine drug metabolism is important for detection of drug abuse in horseracing and also in veterinary drug development and practice. To date, however, no comprehensive review of equine drug metabolism has been published. The majority of literature regarding equine drug metabolite profiles is derived from sports drug detection research and is generally targeted at detecting marker metabolites of drug abuse. However, the bulk of the literature on equine drug metabolism enzymology is derived from veterinary studies aimed at determining the molecular basis of metabolism. In this article, the phase 1 and 2 metabolisms of seven of the most important classes of drugs monitored in horseracing are reviewed, including: anabolic-androgenic steroids (AAS), β2-agonists, stimulants, sedatives/tranquilizers, local anesthetics, non-steroidal anti-inflammatory analgesics (NSAIDS)/cyclooxygenase-2 (COX-2) inhibitors, and opioid analgesics. A summary of the literature relating to the enzymology of drug metabolism in this species is also be presented. The future of equine drug metabolism in the area of doping research will be influenced by several factors, including: a possible move towards the increased use of blood and other alternative testing matrices; the development of assays based on intact drug conjugates; the increasing threat of 'designer' and herbal- based products; advances in the use of in vitro technologies; the increased use of liquid-chromatography/high-resolution mass spectrometry; and the possibility of screening using 'omics' approaches. Also, the recent cloning of a range of equine cytochrome P450 (CYP) enzymes opens up the potential for carrying out more detailed mechanistic pharmacological and toxicological veterinary studies. In this article, the phase one and two metabolism of seven of the most important classes of drugs monitored in horseracing is reviewed. A summary of the literature relating to the enzymology of drug metabolism in this species is also presented. Copyright © 2010 John Wiley & Sons, Ltd.. Source


Scarth J.,A Quotient Bioresearch Ltd Company | Clarke A.,A Quotient Bioresearch Ltd Company | Hands J.,A Quotient Bioresearch Ltd Company | Teale P.,A Quotient Bioresearch Ltd Company | And 2 more authors.
Chromatographia | Year: 2010

A quantitative multi-residue LC- and GC-MS-MS based assay was validated for the analysis of endogenous androgens, progestagens and oestrogens in bovine urine. The method is targeted at analytes indicative of the abuse of nandrolone, boldenone, testosterone, progesterone and oestradiol in cattle. Using a single aliquot of urine, androgens and progestagens are extracted for analysis by GC-MS-MS on a Varian 320 instrument using an enol-TBDMS derivative, while oestrogens are removed into a separate fraction using an extraction derivatisation with dansyl chloride and analysed using LC-MS-MS on a Sciex 5000 instrument. Using a standard addition calibration line approach in pooled bovine urine, the method was found to be sensitive, with limits of detection ranging from 10.9 to 160.7 pg mL-1, and was linear between the endogenous concentrations and those augmented with 3,000 pg mL-1. The method is now being applied to large numbers of animals from controlled populations in order to establish thresholds for detecting the abuse of these steroids in food production. © 2009 Vieweg+Teubner | GWV Fachverlage GmbH. Source

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