NDLI: The use of in vitro technologies coupled with high resolution accurate mass LC-MS for studying drug metabolism in equine drug surveillance.

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The use of in vitro technologies coupled with high resolution accurate mass LC-MS for studying drug metabolism in equine drug surveillance.

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The use of in vitro technologies coupled with high resolution accurate mass LC-MS for studying drug metabolism in equine drug surveillance.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Scarth, James P. Spencer, Holly A. Timbers, Sarah E. Hudson, Simon C. Hillyer, Lynn L.
Description	Country affiliation: United kingdom Author Affiliation: Scarth JP ( HFL Sport Science (A Quotient Bioresearch Ltd Company), Newmarket Road, Fordham, Cambridgeshire, CB7 5WW, UK. jscarth@hfl.co.uk)
Abstract	The detection of drug abuse in horseracing often requires knowledge of drug metabolism, especially if urine is the matrix of choice. In this study, equine liver/lung microsomes/S9 tissue fractions were used to study the phase I metabolism of eight drugs of relevance to equine drug surveillance (acepromazine, azaperone, celecoxib, fentanyl, fluphenazine, mepivacaine, methylphenidate and tripelennamine). In vitro samples were analyzed qualitatively alongside samples originating from in vivo administrations using LC-MS on a high resolution accurate mass Thermo Orbitrap Discovery instrument and by LC-MS/MS on an Applied Biosystems Sciex 5500 Q Trap.Using high resolution accurate mass full-scan analysis on the Orbitrap, the in vitro systems were found to generate at least the two most abundant phase I metabolites observed in vitro for all eight drugs studied. In the majority of cases, in vitro experiments were also able to generate the minor in vivo metabolites and sometimes metabolites that were only observed in vitro. More detailed analyses of fentanyl incubates using LC-MS/MS showed that it was possible to generate good quality spectra from the metabolites generated in vitro. These data support the suggestion of using in vitro incubates as metabolite reference material in place of in vivo post-administration samples in accordance with new qualitative identification guidelines in the 2009 International Laboratory Accreditation Cooperation-G7 (ILAC-G7) document.In summary, the in vitro and in vivo phase I metabolism results reported herein compare well and demonstrate the potential of in vitro studies to compliment, refine and reduce the existing equine in vivo paradigm.
File Format	HTM / HTML
ISSN	19427603
Issue Number	1
Volume Number	2
e-ISSN	19427611
Journal	Drug Testing and Analysis
Language	English
Publisher	Wiley
Publisher Date	2010-01-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Chromatography, Liquid Methods Doping In Sports Prevention & Control Horses Metabolism Mass Spectrometry Pharmaceutical Preparations Animals Female Guidelines As Topic Urine Inactivation, Metabolic Male Microsomes, Liver Reference Standards Substance Abuse Detection Veterinary Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Spectroscopy Environmental Chemistry Analytical Chemistry Pharmaceutical Science

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