期刊
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
卷 22, 期 2, 页码 240-244出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/rcm.3359
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Primary hepatocytes are still the best qualified in vitro system to anticipate drug metabolism in man. Recent advances in hepatocytes cryopreservation have notably increased their use not only for drug metabolism studies, but also for other applications such as cell transplantation. Evaluation of the drug-metabolizing competence of each hepatocytes preparation is needed. To date, the metabolic characterization of hepatocytes preparations relies on the assessment of phase I activities and the role of phase 11 enzymes receives little attention. A novel approach for the rapid assessment of the metabolic functionality of hepatocytes has been developed. A five-probe cocktail was used to simultaneously determine the enzymatic activities of major human phase I CYPs (CYP1A2, CYP2A6, CYP2C9, CYP2E1, CYP3A4), as well as two phase 11 enzymes: glucuronidase (UGTs) and sulfotransferase (SULT). Liquid chromatography/tandem mass spectrometry was used as the technique of choice for the determination of the enzymatic activities in a single run. Results showed that the method described herein permits a rapid assessment of the metabolic capabilities of human hepatocyte preparations as well as an estimation of the quality of freshly isolated or cryopreserved hepatocytes. Copyright (c) 2007 John Wiley & Sons, Ltd.
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