LC/MS/MS for identification of in vivo and in vitro metabolites of jatrorrhizine
LC/MS/MS for identification of in vivo and in vitro metabolites of jatrorrhizine
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DOI：
10.1002/bmc.1066
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发表时间：
2008-12-01
影响因子：
1.8
通讯作者：
Chen, Yong
中科院分区：
文献类型：
--
作者：
Zhang, Yi;Wu, Wenhua;Chen, Yong
采用LC/MS/MS方法研究了药根碱在体内和体外的代谢。用C-18固相萃取柱对健康大鼠灌胃给予药根碱(34 mg/kg)后的大鼠粪便、尿液和血浆样品以及药根碱与大鼠肠道菌群和肝微粒体孵育后的体外样品进行纯化。采用反相C-18色谱柱，以甲醇-甲酸水溶液(70：30，v/v，p H3.5)为流动相，进行在线MS/MS检测，通过与母药的分子质量和产物离子进行比较，对其进行结构鉴定。结果在大鼠尿液中检出7种新的代谢物，在大鼠粪便中检出13种代谢物，在大鼠血浆中检出11种代谢物，在肠道菌群孵育液中鉴定出17种代谢物，在肝微粒体孵育液中检测到9种代谢物。药根碱的生物转化反应主要为母药及其相关代谢产物的羟基化反应、甲基化反应、去甲基化反应和脱氢反应。除大鼠尿液中的部分代谢物外，其余结果均为首次报道。版权所有(C)2008 John Wiley&Sons，Ltd.
The in vivo and in vitro metabolism of jatrorrhizine has been investigated using a specific and sensitive LC/MS/MS method. In vivo samples including rat feces, urine and plasma collected separately after dosing healthy rats with jatrorrhizine (34 mg/kg) orally, along with in vitro samples prepared by incubating jatrorrhizine with rat intestinal flora and liver microsome, respectively, were purified using a C-18 solid-phase extraction cartridge. The purified samples were then separated with a reversed-phase C-18 column with methanol-formic acid aqueous solution (70:30, v/v, pH3.5) as mobile phase and detected by on-line MS/MS. The structural elucidation of the metabolites was performed by comparing their molecular weights and product ions with those of the parent drug. As a result, seven new metabolites were found in rat urine, 13 metabolites were detected in rat feces, 11 metabolites were detected in rat plasma, 17 metabolites were identified in intestinal flora incubation solution and nine metabolites were detected in liver microsome incubation solution. The main biotransformation reactions of jatrorrhizine were the hydroxylation reaction, the methylation reaction, the demethylation reaction and the dehydrogenation reaction of parent drug and its relative metabolites. All the results were reported for the first time, except for some of the metabolites in rat urine. Copyright (C) 2008 John Wiley & Sons, Ltd.