Determination of major human cytochrome P450s activities in 96-well plates using liquid chromatography tandem mass spectrometry
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
- Tipo:
- Article
- Páginas:
- 1247-1252
- PubMed:
- 17521862
- Factor de Impacto:
- 0,723 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
TOXICOLOGY IN VITRO Elsevier BV
Citas Recibidas en Web of Science: 30
Documentos
- No hay documentos
Filiaciones
Filiaciones no disponibles
Proyectos y Estudios Clínicos
DESARROLLO DE UN MODELO HEPATOCELULAR HUMANO DIFERENCIADO PARA ESTUDIOS DE METABOLISMO Y POTENCIAL INDUCTOR DE NUEVOS FARMACOS
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
SAF2003-09353 . 2003
A-CUTE-TOX
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
LSHB-CT-2004-512051-ACUTE TOX . FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2005
DESARROLLO DE NUEVAS ESTRATEGIAS DIAGNOSTICAS BASADAS EN EL ESTUDIO DE LA CAPACIDAD METABOLIZANTE DE LA PIEL Y DEL PAPEL DE LAS CELULAS DENDITRICAS EN LA INDUCCION DE LAS REACCIONES ALERGICAS FRENTE A FARMACOS
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
PARTIC PI05/2290 - FUND IMABIS . INSTITUTO DE SALUD CARLOS III; FUNDACION FIMABIS . 2007
DEVELOPMENT OF A HIGH THROUGHPUT GENOMICS-BASED TEST FOR ASSESSING GENOTOXIC AND CARCINOGENIC PROPERTIES OF CHEMICAL COMPOUNDS IN VITRO
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
CARCINOGENOMICS . COMISION EUROPEA . 2006
LINTOP
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
LSHB-CT-2006-037499 - LINTOP . FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2005
TU HOSPITAL INVESTIGA PARA TI
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
CCT005-07-00936 . 2007