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.

中文翻译：

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通过特定的电化学反应在体内制备Z-ligustilide的关键代谢产物

药物的关键体内代谢产物在其功效和毒性中起着重要作用。然而，由于这些代谢物的含量低且不稳定，因此难以通过体内方法获得。电化学反应可以替代体内生物转化来制备代谢产物。因此，在这项研究中，通过在线与质谱联用的电化学方法在体外研究了Z- ligustilide的代谢。这项工作表明，检测到了五个电化学反应的氧化产物，并且从肝微粒体温育中也鉴定出两个氧化产物（senkyunolide I和senkyunolide H）。此外，在胃内施用Z后在大鼠血浆和肝脏中检出了大鼠中的lig七内酯，senkyunolide I和senkyunolide H，而在体内很难检测到Z -ligustilide的关键中间体代谢物6,7-epoxyligustilide 。相比之下，从电化学反应中获得了6,7-环氧木苷。此外，首次从120 mg的Z -ligustilide制备了6 mg的6,7-环氧木屑。因此，电化学反应代表了制备关键药物代谢物的有效实验室方法。