Assessment of cytochrome P450 induction in human hepatocytes using the cocktail strategy plus liquid chromatography tandem mass spectrometry.
A fast and sensitive method was developed for the assessment of CYP induction in human hepatocytes cultured in 96-well plates. The effects on CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 were examined by means of mass spectrometry and the well-known cocktail strategy. The performance of the method was tested by using prototypic inducers such as methylcolanthrene, phenobarbital and rifampicin. The method was shown to be robust and predictable for the in vitro induction potential studies of drugs.
Unidad Analítica Mixta Fundación, Hospital La Fe-Advancell, Valencia, Spain.
Agustín
A
Lahoz
Maria Teresa
MT
Donato
Laura
L
Picazo
José V
JV
Castell
Maria José
MJ
Gómez-Lechón
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D008748:Methylcholanthrene / Q000494:pharmacology; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D015203:Reproducibility of Results; D012293:Rifampin / Q000494:pharmacology; D053719:Tandem Mass Spectrometry / Q000379:methods*
D004364:Pharmaceutical Preparations; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D012293:Rifampin; D010634:Phenobarbital