Determination of major human cytochrome P450s activities in 96-well plates using liquid chromatography tandem mass spectrometry

Fecha de publicación:

Autores de IIS La Fe

Grupos

Abstract

At the early stage of drug discovery, thousands of new chemical entities (NCEs) may be screened before a single candidate can be identified for development. Evaluation of the effect of NCEs on human CYP450 enzyme activities is a key issue in pharmaceutical development as it may explain inter-subject variability, drug-drug interactions, non-linear pharmacokinetics and toxic effects. A liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method has been developed for the fast and routine analysis of major human CYP450s enzyme activities (CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) in primary hepatocyte cell cultures. The high sensitivity and selectivity of mass spectrometry has allowed traditional assays to be minimized, thus enabling the use of 96-well plate format which markedly reduced the number of hepatocytes needed for each cytochrome CYP450 activity measurement, a fact that is particularly critical concerning human hepatocytes. (C) 2007 Elsevier Ltd. All rights reserved.

Datos de la publicación

ISSN/ISSNe:
0887-2333, 1879-3177

TOXICOLOGY IN VITRO  Elsevier BV

Tipo:
Article
Páginas:
1247-1252
PubMed:
17521862
Factor de Impacto:
0,723 SCImago
Cuartil:
Q1 SCImago

Citas Recibidas en Web of Science: 30

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