Simultaneous determination of morinidazole, its N-oxide, sulfate, and diastereoisomeric N+-glucuronides in human plasma by liquid chromatography-tandem mass spectrometry
文献类型：期刊论文
| 作者 | 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
 |
| 出版日期 | 2012-11-01 |
| 卷号 | 908页码:52-58 |
| ISSN号 | 1570-0232 |
| 关键词 | Liquid chromatography-tandem mass spectrometry Morinidazole Conjugated metabolites N-Oxide metabolite Pharmacokinetics Plasma |
| 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. |
| WOS关键词 | METABOLISM |
| 资助项目 | National Natural Science Foundation of China[81173115] |
| 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 |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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