PMID: identifiant
de la référence Pubmed : |
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 (22579593) |
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| titre : |
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Simultaneous evaluation of six human glucuronidation activities in liver microsomes using liquid chromatography-tandem mass spectrometry. |
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| auteur(s) : |
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Anne-Laure Gagez1, Koukeb Rouguieg-Malki1, François-Ludovic Sauvage1, 2, Pierre Marquet1, 2, Nicolas Picard ( ) 1, 2 |
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| laboratoire : |
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| titre abrégé : |
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Simultaneous evaluation of glucuronidation activities |
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| résumé : |
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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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| domaine : |
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Sciences du Vivant/Pharmacologie/Médicaments
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0003-2697 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1016/j.ab.2012.04.031 |
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| journal : |
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| Analytical Biochemistry (Anal Biochem) |
| Publisher |
Elsevier Masson |
| ISSN |
0003-2697 (eISSN : 1096-0309) |
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| Audience : |
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internationale |
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| date de publication : |
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01/08/2012 |
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date de publication
électronique : |
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10/05/2012 |
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| volume : |
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427 |
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| numéro : |
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1 |
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| page, identifiant, ... : |
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52-9 |
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| mots-clés auteur : |
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"UDP-glucuronosyltransferase" – "microsomes" – "liquid chromatography" – "tandem mass spectrometry" – "drug metabolism" |
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