Rapid and quantitative determination of metabolites from multiple cytochrome P450 probe substrates by gradient liquid chromatography-electrospray ionization-ion trap mass spectrometry.

Tianyi Zhang, Yongxin Zhu, Chandrani Gunaratna

Bioanalytical Systems, Inc, 2701 Kent Avenue, West Lafayette, IN 47906, USA.

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2002 Nov 25

filter terms:

A rapid quantitative assay method, developed by combining fast gradient liquid chromatography and electrospray ionization-ion trap mass spectrometry, is described for the simultaneous determination of CYP450 probe substrate metabolites (4-aminophenol for CYP2E1, acetaminophen for CYP1A2, dextrorphan for CYP2D6, 4'-hydroxymephenytoin for CYP2C19, 4-hydroxytolbutamide for CYP2C9 and 6beta-hydroxytestosterone for CYP3A4) in microsomal incubations. Using this method Michaelis-Menten kinetic parameters K(m) and V(max) for the probe substrates in human liver microsomes were obtained. This LC-MS-MS method, developed with the use of LC-ESI-ion trap MS instrumentation, can efficiently be used to improve the throughput and cost-effectiveness in the preclinical drug metabolism studies. Copyright 2002 Elsevier Science B.V.

Citation

Tianyi Zhang, Yongxin Zhu, Chandrani Gunaratna. Rapid and quantitative determination of metabolites from multiple cytochrome P450 probe substrates by gradient liquid chromatography-electrospray ionization-ion trap mass spectrometry. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2002 Nov 25;780(2):371-9