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Preparing the key metabolite of Z‐ligustilide in vivo by a specific electrochemical reaction

Duan, Feipeng, Xu, Wenjuan, Liu, Jie, Jia, Zhixin, Chen, Kuikui, Chen, Yijun, Wang, Mingxia, Ma, Kaiyue, Dong, Jiaojiao, Chen, Lianming, Xiao, Hongbin
Journal of separation science 2018 v.41 no.13 pp. 2799-2807
biotransformation, drugs, electrochemistry, intragastric administration, laboratory techniques, liver, mass spectrometry, metabolism, metabolites, oxidation, rats, toxicity
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.