Characterization of metabolites of a novel histamine H-2-receptor antagonist, lafutidine, in human liver microsomes by liquid chromatography coupled with ion trap mass spectrometry
文献类型：期刊论文
| 作者 | Wang, Yuya; Chen, Xiaoyan ; Li, Qiang; Zhong, Dafang
|
| 刊名 | RAPID COMMUNICATIONS IN MASS SPECTROMETRY
 |
| 出版日期 | 2008-06 |
| 卷号 | 22期号:12页码:1843-1852 |
| ISSN号 | 0951-4198 |
| DOI | 10.1002/rcm.3558 |
| 文献子类 | Article |
| 英文摘要 | The metabolism of lafutidine in human liver microsomes was studied using liquid chromatography/ion trap mass spectrometry with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources. A total of 14 metabolites were identified including hydroxylated lafutidine and sulfonyl lafutidine as the major metabolites. The chemical properties and the MS' behaviors of lafutidine and all of its identified metabolites were studied in detail. Lafutidine had a fragmentation pattern as a result of homolytic bond cleavage in the MS/MS spectrum. This cleavage can form an odd-electron ion with the loss of furan-2-ylmethyl radical (-81 Da with a proton shift), which then sequentially loses neutral groups in the MS3 spectrum. This fragmentation sequence was also observed from the metabolites with the unchanged sulfinyl moiety. When the sulfinyl moiety was oxidized to the sulfonyl moiety, this fragmentation sequence did not exist, which could be used to identify S-oxidation metabolites of lafutidine. In general, N-oxides could produce distinct [M+H-O](+) ions under LC/APCI-MS due to the thermal activation in the desolvation region of the API source, which could be used to identify N-oxidation metabolites of lafutidine. In order to avoid the possibility of false positives, the MS/MS spectrum of the [M+H-O](+) ion was compared with that of the non-N-oxidation metabolites or parent drug in the APCI source. If they were consistent, the structure could be finally confirmed. The exact masses for lafutidine and lafutidine N-oxide fragment ions were determined using an LTQ/Orbitrap mass spectrometer. Copyright (C) 2008 John Wiley & Sons, Ltd. |
| WOS关键词 | ATMOSPHERIC-PRESSURE IONIZATION ; HUMAN PLASMA ; N-OXIDES ; GASTROPROTECTIVE ACTIVITY ; IDENTIFICATION ; MS |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Spectroscopy |
| 语种 | 英语 |
| WOS记录号 | WOS:000256985100010 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272915]  |
| 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 | Wang, Yuya,Chen, Xiaoyan,Li, Qiang,et al. Characterization of metabolites of a novel histamine H-2-receptor antagonist, lafutidine, in human liver microsomes by liquid chromatography coupled with ion trap mass spectrometry[J]. RAPID COMMUNICATIONS IN MASS SPECTROMETRY,2008,22(12):1843-1852. |
| APA | Wang, Yuya,Chen, Xiaoyan,Li, Qiang,&Zhong, Dafang.(2008).Characterization of metabolites of a novel histamine H-2-receptor antagonist, lafutidine, in human liver microsomes by liquid chromatography coupled with ion trap mass spectrometry.RAPID COMMUNICATIONS IN MASS SPECTROMETRY,22(12),1843-1852. |
| MLA | Wang, Yuya,et al."Characterization of metabolites of a novel histamine H-2-receptor antagonist, lafutidine, in human liver microsomes by liquid chromatography coupled with ion trap mass spectrometry".RAPID COMMUNICATIONS IN MASS SPECTROMETRY 22.12(2008):1843-1852. |
入库方式： OAI收割
来源：上海药物研究所
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