Humantenirine is an active oxindole alkaloid extracted from Gelsemium elegans Benth (G. elegans). In the present study, the metabolites of humantenirine in liver microsomes were first identified by HPLC/QqTOF-MS. Then, the metabolic profile and tissue distribution after oral administration in rats were further investigated. A total of seven metabolites were identified in vitro, and five metabolites in vitro were found in vivo. Moreover, a Ⅱ-phase metabolite was identified first in vivo. The results indicated that humantenirine could be metabolized widely. The parent drug and its metabolites were distributed widely in various tissues and highly in the liver and pancreas. However, the parent drug and its metabolites had low peak intensities in plasma. The elimination of humantenirine occurred rapidly as well, the most unconverted forms of which were found in the kidney. Metabolic pathways, including demethylation, dehydrogenation, oxidation and glucuronidation, were proposed. The present findings may provide a basis for the study of pharmacokinetic characteristics and will contribute to the evaluation of the pharmacology and toxicity of G. elegans.

Humantenirine 是一种从Gelsemium elegans Benth ( G. elegans ) 中提取的活性羟吲哚生物碱。在本研究中，首先通过HPLC/QqTOF-MS鉴定了肝微粒体中人替尼林的代谢物。然后，进一步研究大鼠口服给药后的代谢特征和组织分布。体外共鉴定出7种代谢物，体内发现5种体外代谢物。此外，首先在体内鉴定出一种Ⅱ期代谢物. 结果表明，humantenirine 可广泛代谢。母体药物及其代谢物广泛分布于各种组织中，在肝脏和胰腺中分布高度。然而，母体药物及其代谢物在血浆中的峰强度较低。humantenirine 的消除也很快发生，其中最未转化的形式是在肾脏中发现的。提出了代谢途径，包括去甲基化、脱氢、氧化和葡萄糖醛酸化。目前的研究结果可能为药代动力学特征的研究提供基础，并将有助于评估G. elegans的药理学和毒性。