Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jpba.2013.09.006
Title: Simultaneous determination of probe drugs, metabolites, inhibitors and inducer in human plasma by liquid chromatography/tandem mass spectrometry and its application to pharmacokinetic study
Authors: Hee, K.H. 
Yao, Z.
Lee, L.S. 
Keywords: Ketoconazole
Midazolam
Raltegravir
Rifampin
Ritonavir
Issue Date: 25-Jan-2014
Citation: Hee, K.H., Yao, Z., Lee, L.S. (2014-01-25). Simultaneous determination of probe drugs, metabolites, inhibitors and inducer in human plasma by liquid chromatography/tandem mass spectrometry and its application to pharmacokinetic study. Journal of Pharmaceutical and Biomedical Analysis 88 : 584-593. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jpba.2013.09.006
Abstract: Cytochrome P450 3A4 (CYP3A4) and UDP-glucuronosyltransferase 1A1 (UGT1A1) are important enzymes responsible for the metabolism of many xenobiotics. To investigate their induction and inhibition properties, administering probe drugs and monitoring their concentration in plasma under the effects of inducers/inhibitors is the gold standard method. A rapid and sensitive liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of midazolam, raltegravir (probe drugs for CYP3A4 and UGT1A1), their major metabolites, 1'-hydroxymidazolam, 1'-hydroxymidazolam glucuronide and raltegravir glucuronide, rifampicin (inducer), ritonavir and ketoconazole (inhibitors). Analytes were extracted from 100μl of plasma using solid-phase extraction followed by chromatographic separation on a reversed-phase C18 column (50mm×2.1mm, particle size 1.8μm). The mass spectrometer was operated under positive ionization mode. Excellent linearity (r2≥0.995) was achieved for all. The method was validated and found to be accurate (88-111%), precise (CV%
Source Title: Journal of Pharmaceutical and Biomedical Analysis
URI: http://scholarbank.nus.edu.sg/handle/10635/126856
ISSN: 07317085
DOI: 10.1016/j.jpba.2013.09.006
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