Murpanicin is a main coumarin with obvious anti-inflammatory effect isolated from Murraya species. The primary aim of this research is to identify and characterize the possible metabolites of murpanicin in rats. The metabolites generated in the plasma, urine, bile, and feces of rats were identified and characterized employing ultra-high performance liquid chromatography coupled with quadrupole-time of flight tandem mass spectrometry (UHPLC/Q-TOF-MS/MS) based on diagnostic fragment ions (DFIs) and multiple mass defect filter (MMDF). A total of 67 metabolites were identified, among which 55 are phase I and 12 are phase II reacted products. The plausible structures of the metabolites and the probable metabolic pathways were deduced based on the diagnostic fragment ions, mass ppm error, and mass fragmentation pattern, as well as the MetabolitePilot™ software. The majority of phase I metabolites were generated by demethylation, deethylation, dehydrogenation, hydroxylation, and reduction, while phase II metabolites were mainly generated by glucuronidation and sulfation. Moreover, some rare phase II metabolic pathways, such as N-acetylcysteine conjugation, cysteine conjugation, and S-cysteine conjugation were also observed. In conclusion, our study first expounded the metabolites of murpanicin in rats and provided reference for further clarification of the in vivo therapeutic material basis of murpanicin and other 8-prenylcoumarin derivatives. Moreover, UHPLC/Q-TOF-MS combined with MMDF and DFIs has been proved to be an effective method for rapid identification of the homolog-gathered natural products and their metabolites.

Murpanicin 是从Murraya中分离出来的具有明显抗炎作用的主要香豆素物种。本研究的主要目的是鉴定和表征大鼠中莫帕尼星的可能代谢物。采用基于诊断的超高效液相色谱结合四极杆飞行时间串联质谱 (UHPLC/Q-TOF-MS/MS) 对大鼠血浆、尿液、胆汁和粪便中产生的代谢物进行鉴定和表征碎片离子 (DFI) 和多质量缺陷过滤器 (MMDF)。共鉴定出 67 种代谢物，其中 55 种为 I 期反应产物，12 种为 II 期反应产物。基于诊断碎片离子、质量 ppm 误差和质量碎片模式以及 MetabolitePilot™ 软件推导出代谢物的合理结构和可能的代谢途径。大多数 I 期代谢物是通过去甲基化产生的，去乙基化、脱氢、羟基化和还原，而 II 相代谢物主要由葡萄糖醛酸化和硫酸化生成。此外，一些罕见的 II 期代谢途径，如还观察到N-乙酰半胱氨酸缀合、半胱氨酸缀合和S-半胱氨酸缀合。综上所述，本研究首次阐明了莫帕尼星在大鼠体内的代谢产物，为进一步阐明莫帕尼星等8-异戊二烯基香豆素衍生物的体内治疗物质基础提供了参考。此外，UHPLC/Q-TOF-MS 结合 MMDF 和 DFI 已被证明是快速鉴定同源物聚集的天然产物及其代谢物的有效方法。