Simultaneous evaluation of six human glucuronidation activities in liver microsomes using liquid chromatography-tandem mass spectrometry

Analytical Biochemistry
Anne-Laure GagezNicolas Picard

Abstract

This article describes the development of a procedure for the simultaneous evaluation of the activity of six different uridine diphosphate (UDP)-glucuronyltransferases (UGTs) in human liver microsomes (HLMs). The method consists of incubations of probe substrates for UGT1A1 (etoposide), UGT1A3 (chenodeoxycholic acid), UGT1A4 (trifluoperazine), UGT1A6 (serotonin), UGT1A9 (mefenamic acid), and UGT2B7 (azidothymidine) with HLMs. The six substrates were divided into three different incubations (etoposide + mefenamic acid; chenodeoxycholic acid + serotonin + azidothymidine; and trifluoperazine alone), the media of which were pooled before analysis. Glucuronide formation rates were determined in a single run of 20 min using a validated liquid chromatography-tandem mass spectrometry method. No significant difference was observed between glucuronidation activities measured using the current procedure and individual incubations of the probes. The method was used successfully for the determination of UGT activities in 44 individual HLM preparations and for the phenotyping of preparations predicted to have altered UGT1A1 and UGT2B7 activities because of known genetic polymorphisms.

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Citations

Dec 29, 2013·European Journal of Drug Metabolism and Pharmacokinetics·Jin-Fang XiaoHai-Hong Fang
Feb 28, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Shalenie P den Braver-SewradjJ Chris Vos
Oct 11, 2014·Rapid Communications in Mass Spectrometry : RCM·Jeongmin JooKwang-Hyeon Liu
Feb 17, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Julieta GradinaruSerge Rudaz
Dec 12, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Alaa Al SaabiNicolas Picard

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