识别ultraperformance胺碘酮在人胆汁代谢物的液相色谱/四极飞行时间质谱分析。

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陈邓P T, X,钟元T,黄H, D

识别ultraperformance胺碘酮在人胆汁代谢物的液相色谱/四极飞行时间质谱分析。

药物金属底座Dispos。2011年6月,39 (6):1058 - 69。doi: 10.1124 / dmd.110.037671。Epub 2011年3月11日。

PubMed ID

21398391 (在PubMed

]

文摘

胺碘酮被认为是一个有效的药物治疗心律失常。先前的实验表明,mono-N-desethylamiodarone (MDEA)是人类的主要循环代谢物。此外,脱烷基化作用、羟基化和脱氨基作用是次要的代谢途径。本研究的目的是确定胺碘酮在胆汁的代谢物从患者获得丁字管排水后口服药物管理局。胺碘酮代谢体外也调查了使用人类肝脏微粒体(高)和S9分数。Ultraperformance液相色谱/四极飞行时间质谱(UPLC-Q / TOF MS)显示33人类胆汁代谢物,包括22期和11个二期代谢物。的主要代谢物MDEA M7和omega-carboxylate胺碘酮(M12)。从人类胆汁代谢物M12分离,化学结构确认使用UPLC-Q / TOF MS和(1)H NMR。此外,两个羟化代谢产物的真实标准,2-hydroxylamiodarone和3 ' -hydroxylamiodarone,通过微生物转化。提出了一些新颖的代谢途径的胺碘酮在人类,包括omega-carboxylation deiodination, glucuronidation。 The in vitro study demonstrated that incubation of HLMs with amiodarone did not give rise to any carboxyl metabolites. In contrast, M12 and its metabolites were detected in human liver S9 incubation samples, and the production of these metabolites were inhibited almost completely by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, suggesting the involvement of alcohol dehydrogenase in the omega-carboxylation of amiodarone. Overall, UPLC-Q/TOF MS analysis leads to the discovery of several novel amiodarone metabolites in human bile and underscores the importance of bile as an excretion pathway.

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药物

胺碘酮