caa a22 4500 445801115 CHVBK 20180317145141.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10337-010-1882-5 doi (NATIONALLICENCE)springer-10.1007/s10337-010-1882-5 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 [Elektronische Daten] [Kwon-Bok Kim, Hyunmi Kim, Fen Jiang, Chang-Woo Yeo, Soo Bae, Zeruesenay Desta, Jae-Gook Shin, Kwang-Hyeon Liu] 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 0.1M sodium carbonate after incubation of β-glucuronidase (500U). After drying the organic layer, the residue was reconstituted in mobile phase (acetonitrile:20mM ammonium acetate, 90:10, v/v) and injected onto a reversed-phase C18 column. The isocratic mobile phase was eluted at 0.2mLmin−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 1.82min 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 5ngmL−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 600mg oral dose of efavirenz. This analytical method is a very rapid, sensitive, and accurate to determine the pharmacokinetic profiles of efavirenz including its metabolites. Springer-Verlag, 2011 Column liquid chromatography-tandem mass spectrometry nationallicence Efavirenz nationallicence 8-Hydroxyefavirenz nationallicence 8,14-Dihydroxyefavirenz nationallicence Human plasma nationallicence Kim Kwon-Bok Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut Kim Hyunmi Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut Jiang Fen Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut Yeo Chang-Woo Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut Bae Soo Department of Clinical Pharmacology and Clinical Trial Center, Inje University Busan Paik Hospital, 614-735, Busan, South Korea aut Desta Zeruesenay Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 1001 West 10th Street, WD Myers Bldg., W7123, 46202, Indianapolis, IN, USA aut Shin Jae-Gook Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut Liu Kwang-Hyeon Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut Chromatographia Vieweg Verlag 73/3-4(2011-02-01), 263-271 0009-5893 73:3-4<263 2011 73 10337 https://doi.org/10.1007/s10337-010-1882-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10337-010-1882-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kim Kwon-Bok Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut NATIONALLICENCE 700 1- Kim Hyunmi Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut NATIONALLICENCE 700 1- Jiang Fen Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut NATIONALLICENCE 700 1- Yeo Chang-Woo Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut NATIONALLICENCE 700 1- Bae Soo Department of Clinical Pharmacology and Clinical Trial Center, Inje University Busan Paik Hospital, 614-735, Busan, South Korea aut NATIONALLICENCE 700 1- Desta Zeruesenay Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 1001 West 10th Street, WD Myers Bldg., W7123, 46202, Indianapolis, IN, USA aut NATIONALLICENCE 700 1- Shin Jae-Gook Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut NATIONALLICENCE 700 1- Liu Kwang-Hyeon Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 614-735, Busan, South Korea aut NATIONALLICENCE 773 0- Chromatographia Vieweg Verlag 73/3-4(2011-02-01), 263-271 0009-5893 73:3-4<263 2011 73 10337 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer