Simultaneous determination of morinidazole, its N-oxide, sulfate, and diastereoisomeric N+-glucuronides in human plasma by liquid chromatography-tandem mass spectrometry

doi:10.1016/j.jchromb.2012.09.017

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	Simultaneous determination of morinidazole, its N-oxide, sulfate, and diastereoisomeric N+-glucuronides in human plasma by liquid chromatography-tandem mass spectrometry
	Gao, Ruina; Zhong, Dafang; Liu, Ke; Xia, Yu; Shi, Rongwei; Li, Hua; Chen, Xiaoyan
刊名	JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
	2012-11-01
卷号	908 页码:52-58
关键词	Liquid chromatography-tandem mass spectrometry Morinidazole Conjugated metabolites N-Oxide metabolite Pharmacokinetics Plasma
ISSN号	1570-0232
DOI	10.1016/j.jchromb.2012.09.017
文献子类	Article
英文摘要	Morinidazole is a new third-generation 5-nitroimidazole antimicrobial drug. To investigate the pharmacokinetic profiles of morinidazole and its major metabolites in humans, a liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of morinidazole, its N-oxide metabolite (M4-1), a sulfate conjugate (M7), and two diastereoisomeric N+-glucuronides (M8-1 and M8-2) in human plasma. A simple acetonitrile-induced protein precipitation was employed to extract five analytes and internal standard metronidazole from 50 mu L human plasma. To avoid the interference from the in-source dissociation of the sulfate and achieve the baseline-separation of diastereoisomeric N+-glucuronides, all the analytes were separated from each other with the mobile phase consisting of 10 mM ammonium formate and acetonitrile using gradient elution on a Hydro-RP C-18 column (50 mm x 2 mm, 4 mu m) with a total run time of 5 min. The API 4000 triple quadrupole mass spectrometer was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. The developed method was linear in the concentration ranges of 10.0-12,000 ng/mL for morinidazole, 1.00-200 ng/mL for M4-1, 2.50-500 ng/mL for M7, 3.00-600 ng/mL for M8-1, and 10.0-3000 ng/mL for M8-2. The intra- and inter-day precisions for each analyte met the accepted value. Results of the stability of morinidazole and its metabolites in human plasma were also presented. The method was successfully applied to the clinical pharmacokinetic studies of morinidazole injection in healthy subjects, patients with moderate hepatic insufficiency, and patients with severe renal insufficiency, respectively. (C) 2012 Elsevier BM. All rights reserved.
资助项目	National Natural Science Foundation of China[81173115]
WOS关键词	METABOLISM
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000311195100008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277886]
专题	上海药物代谢研究中心
通讯作者	Chen, Xiaoyan
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	Gao, Ruina,Zhong, Dafang,Liu, Ke,et al. Simultaneous determination of morinidazole, its N-oxide, sulfate, and diastereoisomeric N+-glucuronides in human plasma by liquid chromatography-tandem mass spectrometry[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2012,908:52-58.
APA	Gao, Ruina.,Zhong, Dafang.,Liu, Ke.,Xia, Yu.,Shi, Rongwei.,...&Chen, Xiaoyan.(2012).Simultaneous determination of morinidazole, its N-oxide, sulfate, and diastereoisomeric N+-glucuronides in human plasma by liquid chromatography-tandem mass spectrometry.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,908,52-58.
MLA	Gao, Ruina,et al."Simultaneous determination of morinidazole, its N-oxide, sulfate, and diastereoisomeric N+-glucuronides in human plasma by liquid chromatography-tandem mass spectrometry".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 908(2012):52-58.