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[摘要]
目的 采用UPLC-Q-TOF-MS/MS研究腰痹通胶囊在大鼠尿液和胆汁中的代谢产物,并归纳主要代谢途径。方法 通过空白对照法寻找尿液和胆汁中可能的代谢产物,依据所获得的精确相对分子质量和二级碎片离子对代谢产物进行推测。结果 在正、负离子模式下尿液中共检测到31个代谢产物,胆汁中共检测到35个代谢产物,主要为藁本内酯、3-丁基苯酞、蛇床子素、洋川芎内酯A、川芎内酯A、大黄素、紫花前胡醇或紫花前胡苷元或二氢山芹醇、紫堇杷明碱或异紫堇杷明碱、紫堇鳞茎碱或异紫堇鳞茎碱或元胡菲碱、别隐品碱、阿魏酸、隐绿原酸、当归醇类等化合物的I相或Ⅱ相代谢产物,主要代谢途径为内酯环水解、羟基化、去甲基、脱水、脱氢、脱羟基、氢化、甲基化、甲基氧化、葡萄糖醛酸化、硫酸酯化、N-乙酰半胱氨酸结合、半胱氨酸结合、半胱氨酸-甘氨酸结合、谷胱甘肽结合等。此外,胆汁中检测到3个原型成分,即芍药苷、芍药内酯苷和人参皂苷Rg1。结论 建立的UPLC-Q-TOF-MS/MS方法能够分析出腰痹通胶囊在大鼠尿液和胆汁中的代谢产物,初步阐明了腰痹通胶囊的体内代谢特征,为腰痹通胶囊在体内发挥疗效的药效物质基础研究提供了依据。
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[Abstract]
Objective The main metabolites of Yaobitong Capsule (YC) in rat urine and bile were investigated by UPLC-Q-TOF-MS/MS, and their major metabolic pathways were summarized. Methods To compare with the control samples, the possible metabolites were found. Their structures were speculated by exact mass and fragment ions. Results YC had 31 metabolites in urine and 35 metabolites in bile under positive and negative ion mode. They were mainly the metabolites of ligustilide, 3-butyl-phthalide, osthole, senkyunolide A, sankyunolide A, emodin, decursinol/marmesin/columbianetin, corypalmine/isocorypalmine, corybulbine/isocorybulbine/coryphenanthrine, allocryptopine, ferulic acid, cryptochlorogenic acid, angelol and so on. Their major metabolic pathways included hydrolysis of the lactone ring, hydroxylation, demethylation, dehydration, dehydrogenation, dehydroxylation, hydrogenation, methylation, methyl oxidation, glucuronidation, sulphate-binding, N-acetylcysteine-binding, cysteine-binding, cysteinyl acid-glycine-binding, glutathione-binding and so on. In addition, three prototype components, namely paeoniflorin, albiflorin, and ginsenosides Rg1, were detected in rats' bile. Conclusion The established UPLC-Q-TOF-MS/MS method can analyze the metabolites of YC capsule in rat urine and bile. The in vivo metabolic characteristics of YC have been initially clarified. The results provide a foundation for elucidating the in vivo efficacy ingredients of YC.
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