Characterization of metabolites of GLS4 in humans using ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry

doi:10.1002/rcm.6710

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	Characterization of metabolites of GLS4 in humans using ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry
	Zhou, Xin; Li, Liang; Deng, Pan; Chen, Xiaoyan; Zhong, Dafang
刊名	RAPID COMMUNICATIONS IN MASS SPECTROMETRY
	2013-11-15
卷号	27 期号:21 页码:2483-2492
ISSN号	0951-4198
DOI	10.1002/rcm.6710
文献子类	Article
英文摘要	RATIONALEGLS4 is a heteroaryldihydropyrimidine compound that inhibits hepatitis B virus (HBV) replication by drug-induced depletion of nucleocapsids. It is currently undergoing clinical trials in China to treat HBV infection. The aim of this study was to identify the metabolites of GLS4 in humans. METHODSA rapid and sensitive method based on ultrahigh-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry was used to identify GLS4 metabolites in human plasma, urine, and feces after an oral dose of 120mg GLS4. RESULTSA total of 27 metabolites were detected and identified by comparing the accurate molecular masses, retention times and spectral patterns of the analytes with those of the parent drug. Nine metabolites were confirmed by comparison with reference substances. All of the metabolites had a bromine atom and displayed the isotope ion of [M+H](+)/[M+H+2](+) at a ratio of 1:1. Fragmentation of the dihydropyrimidine structure was characterized by the loss of the m-bromofluorobenzene group to generate an ion at m/z 220.0175. The morpholine ring was characterized by an ion at m/z 100.0757. CONCLUSIONSThe metabolites of GLS4 in humans were identified by the diagnostic ions of dihydropyrimidine and morpholine rings. GLS4 underwent extensive dealkylation, hydrolysis, dehydrogenation, oxidation, and glucuronidation reactions in humans. Copyright (c) 2013 John Wiley & Sons, Ltd.
WOS关键词	IDENTIFICATION ; URINE
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry ; Spectroscopy
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000325254300022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277377]
专题	上海药物代谢研究中心
通讯作者	Zhong, Dafang
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Xin,Li, Liang,Deng, Pan,et al. Characterization of metabolites of GLS4 in humans using ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry[J]. RAPID COMMUNICATIONS IN MASS SPECTROMETRY,2013,27(21):2483-2492.
APA	Zhou, Xin,Li, Liang,Deng, Pan,Chen, Xiaoyan,&Zhong, Dafang.(2013).Characterization of metabolites of GLS4 in humans using ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.RAPID COMMUNICATIONS IN MASS SPECTROMETRY,27(21),2483-2492.
MLA	Zhou, Xin,et al."Characterization of metabolites of GLS4 in humans using ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry".RAPID COMMUNICATIONS IN MASS SPECTROMETRY 27.21(2013):2483-2492.