NDLI: Rapid and Simultaneous Determination of Efavirenz, 8-Hydroxyefavirenz, and 8,14-Dihydroxyefavirenz Using LC–MS–MS in Human Plasma and Application to Pharmacokinetics in Healthy Volunteers

Content Provider	Springer Nature Link
Author	Kim, Kwon Bok Kim, Hyunmi Jiang, Fen Yeo, Chang Woo Bae, Soo Kyung Desta, Zeruesenay Shin, Jae Gook Liu, Kwang Hyeon
Copyright Year	2011
Abstract	We developed a rapid and sensitive method for determining efavirenz, 8-hydroxyefavirenz, and 8,14-dihydroxyefavirenz in human plasma simultaneously using liquid chromatography–tandem mass spectrometry (LC–MS–MS). Three compounds and ritonavir, an internal standard, were extracted from plasma using ethyl acetate in the presence of 0.1 M sodium carbonate after incubation of β-glucuronidase (500 U). After drying the organic layer, the residue was reconstituted in mobile phase (acetonitrile:20 mM ammonium acetate, 90:10, v/v) and injected onto a reversed-phase C18 column. The isocratic mobile phase was eluted at 0.2 mL min−1. The ion transitions monitored in multiple reaction-monitoring mode were m/z 314 → 244, 330 → 258, 346 → 262, and 721 → 296 for efavirenz, 8-hydroxyefavirenz, 8,14-dihydroxyefavirenz, and ritonavir, respectively. The retention time is 1.93, 1.70, 1.52, and 1.82 min for efavirenz, 8-hydroxyefavirenz, 8,14-dihydroxyefavirenz, and ritonavir, respectively. The coefficients of variation of the assay precision were less than 10.7%, and the accuracy was 90–111%. The lower limits of quantification (LLOQ) were 5 ng mL−1 for efavirenz and 8-hydroxyefavirenz. This method was used to measure the plasma concentrations of efavirenz and its metabolites from healthy volunteers after a single 600 mg oral dose of efavirenz. This analytical method is a very rapid, sensitive, and accurate to determine the pharmacokinetic profiles of efavirenz including its metabolites.
Starting Page	263
Ending Page	271
Page Count	9
File Format	PDF
ISSN	00095893
Journal	Chromatographia
Volume Number	73
Issue Number	3-4
e-ISSN	16121112
Language	English
Publisher	Vieweg Verlag
Publisher Date	2011-01-09
Publisher Place	Wiesbaden
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Column liquid chromatography–tandem mass spectrometry Efavirenz 8-Hydroxyefavirenz 8,14-Dihydroxyefavirenz Human plasma Measurement Science and Instrumentation Plant Sciences Biochemistry Pharmacy Organic Chemistry Analytical Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Analytical Chemistry Biochemistry Clinical Biochemistry

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