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A sensitive and specific liquid chromatography/tandem mass spectrometry method for quantification of nevirapine and its five metabolites and their pharmacokinetics in baboons
Author(s) -
Ren Chen,
FanHavard Patty,
SchlabritzLoutsevitch Natalia,
Ling Yonghua,
Chan Kenneth K.,
Liu Zhongfa
Publication year - 2010
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1353
Subject(s) - pharmacokinetics , chemistry , chromatography , nevirapine , metabolite , baboon , mass spectrometry , pharmacology , human immunodeficiency virus (hiv) , biochemistry , virology , medicine , antiretroviral therapy , viral load , biology
A highly sensitive and specific LC‐MS/MS assay was developed and validated to quantify nevirapine (NVP) and its five metabolites [2‐, 3‐, 8‐, 12‐hydroxyl NVP (OHNVP) and 4‐carboxyl NVP (CANVP)] simultaneously in baboon serum and the assay was used to characterize their pharmacokinetic studies of an oral‐dose escalation study in baboon. The lower limit of quantification (LLOQ) for NVP and its four hydroxyl nevirapine metabolites was 1.0 ng/mL and for 4‐CANVP was 5.0 ng/mL. The between‐run and within‐run precisions and accuracies at four quality control concentrations (1, 5, 50 and 500 ng/mL) were evaluated in baboon serum with less than 14% variation and 93–114% accuracies ( n = 6), except for the LLOQ for 2‐OHNVP, which had an accuracy of 115.8% for between‐run validation. The pharmacokinetics of NVP and its five metabolites in non‐pregnant baboons by a single‐dose escalation study were also profiled. The major metabolites detected were 4‐CANVP and 12‐OHNVP. 3‐OHNVP and 2‐OHNVP were the minor metabolites with only a trace amount of 2‐OHNVP detected in some pharmacokinetic samples. No 8‐OHNVP was observed in all of the pharmacokinetic samples. In addition, the fragmentation for the four hydroxyl metabolite isomers is also discussed. Copyright © 2009 John Wiley & Sons, Ltd.