Preparing the key metabolite of Z-ligustilide in vivo by a specific electrochemical reaction
Preparing the key metabolite of Z-ligustilide in vivo by a specific electrochemical reaction
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通过特定的电化学反应制备Z-藁本内酯体内关键代谢物
DOI：
10.1002/jssc.201800164
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发表时间：
2018-07-01
影响因子：
3.1
通讯作者：
Xiao, Hongbin
中科院分区：
文献类型：
--
作者：
Duan, Feipeng;Xu, Wenjuan;Xiao, Hongbin
药物的关键体内代谢物在其疗效和毒性方面起着重要作用。然而，由于这些代谢物含量低且不稳定，通过体内方法很难获得。电化学反应可以作为体内生物转化制备代谢物的一种有效替代方法。因此，在本研究中，通过电化学与质谱在线联用的方法在体外研究了藁本内酯的代谢。这项工作表明，检测到了电化学反应的五种氧化产物，并且从肝微粒体孵育中也鉴定出了其中两种氧化产物（洋川芎内酯I和洋川芎内酯H）。此外，在大鼠灌胃给予藁本内酯后，在大鼠血浆和肝脏中检测到了洋川芎内酯I和洋川芎内酯H，而藁本内酯的关键中间代谢物6,7 - 环氧藁本内酯在体内难以检测到。相比之下，6,7 - 环氧藁本内酯可通过电化学反应获得。此外，首次从120mg藁本内酯制备出了6mg的6,7 - 环氧藁本内酯。因此，电化学反应是一种制备关键药物代谢物的有效实验室方法。
The key in vivo metabolites of a drug play an important role in its efficacy and toxicity. However, due to the low content and instability of these metabolites, they are hard to obtain through in vivo methods. Electrochemical reactions can be an efficient alternative to biotransformation in vivo for the preparation of metabolites. Accordingly, in this study, the metabolism of Z-ligustilide was investigated in vitro by electrochemistry coupled online to mass spectrometry. This work showed that five oxidation products of the electrochemical reaction were detected and that two of the oxidation products (senkyunolide I and senkyunolide H) were identified from liver microsomal incubation as well. Furthermore, after intragastric administration of Z-ligustilide in rats, senkyunolide I and senkyunolide H were detected in the rat plasma and liver, while 6,7-epoxyligustilide, a key intermediate metabolite of Z-ligustilide, was difficult to detect in vivo. By contrast, 6,7-epoxyligustilide was obtained from the electrochemical reaction. In addition, for the first time, 6 mg of 6,7-epoxyligustilide was prepared from 120 mg of Z-ligustilide. Therefore, electrochemical reactions represent an efficient laboratory method for preparing key drug metabolites.