title: Rapid identification of efavirenz metabolites in rats and humans by ultra high performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry.
abstract: An in vivo study of efavirenz metabolites in rats and human patients with ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry combined with MetabolitePilot(MT) software is reported for the first time. Considering the polarity differences between the metabolites, solid-phase extraction and protein precipitation were both applied as a part of the sample preparation method. The structures of the metabolites and their fragment ions were identified or tentatively characterized based on the accurate mass and MS(2) data. As a result, a total of 15 metabolites, including 11 from rat samples and 13 from human samples, were identified or tentatively characterized. Two metabolites and several new metabolism pathways are reported for the first time. This study provides a practical approach for identifying complicated metabolites through the rapid and reliable ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry technique, which could be widely used for the investigation of drug metabolites.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, P. R. China.
authors.forename: Yachen
authors.initials: Y
authors.lastname: Deng
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, P. R. China.|Shanghai Public Clinical Health Centre, Shanghai, P. R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, P. R. China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Liang
mesh_terms: D000480:Alkynes; D000818:Animals; D048588:Benzoxazines / Q000737:chemistry / Q000378:metabolism* / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D006801:Humans; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz
keywords: Efavirenz; High-resolution mass spectrometry; Human urine; Metabolite identification; Rat urine