Rapid and quantitative determination of metabolites from multiple cytochrome P450 probe substrates by gradient liquid chromatography-electrospray ionization-ion trap mass spectrometry.
Article Details
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Zhang T, Zhu Y, Gunaratna C
Rapid and quantitative determination of metabolites from multiple cytochrome P450 probe substrates by gradient liquid chromatography-electrospray ionization-ion trap mass spectrometry.
J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 25;780(2):371-9.
- PubMed ID
- 12401364 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Dextromethorphan Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails Mephenytoin Cytochrome P450 2C19 Protein Humans UnknownSubstrateInhibitorDetails Phenacetin Cytochrome P450 1A2 Protein Humans UnknownSubstrateDetails Testosterone Cytochrome P450 3A4 Protein Humans UnknownSubstrateInducerDetails Testosterone cypionate Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorInducerDetails Testosterone enanthate Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorInducerDetails Testosterone undecanoate Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorInducerDetails