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利用 UHPLC-Q-exactive 轨道阱质谱仪鉴定大鼠中的道利司啉代谢物。

Identification of daurisoline metabolites in rats via the UHPLC-Q-exactive orbitrap mass spectrometer.

机构信息

Department of Pharmacy, Shanghai General Hospital Jiuquan Hospital (The People's Hospital of Jiuquan), Jiuquan, GanSu 735000, China.

Department of Pharmacy, Shanghai General Hospital Jiuquan Hospital (The People's Hospital of Jiuquan), Jiuquan, GanSu 735000, China.

出版信息

J Pharm Biomed Anal. 2025 Jan 1;252:116482. doi: 10.1016/j.jpba.2024.116482. Epub 2024 Sep 19.

Abstract

Daurisoline, a bisbenzylisoquinoline alkaloid extracted from the rhizomes of Menispermum dauricum, exhibits diverse biological activities, encompassing antiplatelet, anti-inflammatory, neuroprotective, and antitumor properties. However, previous investigations have not comprehensively elucidated the metabolic profile and pathways of daurisoline in vivo. Using Ultra-High-Performance Liquid Chromatography with Q-Exactive Orbitrap Mass Spectrometry technology, we comprehensively investigated the metabolites of daurisoline in Sprague-Dawley rats, following intragastric administration. Data collection and analysis were enhanced through Full Scan MS/dd-MS, in conjunction with parallel reaction monitoring, extracted ion chromatography, and diagnostic fragment ions. Sixty-three metabolites were detected and characterized, including sixty-two novel metabolites and coclaurine. This investigation elucidated the cleavage patterns and tissue distribution characteristics of the metabolism of daurisoline. Furthermore, in vivo reactions, including dehydrogenation, hydroxylation, methylation, sulfation and glucuronidation, were thoroughly examined. Investigating the metabolites of daurisoline in rats has deepened our understanding of its metabolism in vivo, aiding in elucidating its metabolic and pharmacological actions. This provides a valuable foundation for further research into its therapeutic efficacy.

摘要

蝙蝠葛苏林碱,一种从蝙蝠葛根茎中提取的双苄基异喹啉生物碱,具有多种生物活性,包括抗血小板、抗炎、神经保护和抗肿瘤作用。然而,以前的研究并没有全面阐明蝙蝠葛苏林碱在体内的代谢谱和途径。本研究采用超高效液相色谱- Q- Exactive 轨道阱质谱联用技术,全面研究了蝙蝠葛苏林碱在灌胃给予 Sprague-Dawley 大鼠后的体内代谢物。通过全扫描 MS/dd-MS 与平行反应监测、提取离子色谱和诊断碎片离子相结合,增强了数据的采集和分析。共检测到 63 种代谢物,包括 62 种新型代谢物和蝙蝠葛苏林碱。本研究阐明了蝙蝠葛苏林碱的代谢裂解模式和组织分布特征。此外,还深入研究了体内的反应,包括脱氢、羟化、甲基化、硫酸化和葡萄糖醛酸化。研究大鼠体内蝙蝠葛苏林碱的代谢物,加深了我们对其体内代谢的理解,有助于阐明其代谢和药理作用。这为进一步研究其治疗效果提供了有价值的基础。

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