LC-MS/MS法测定大鼠血浆中夏枯草消瘤合剂有效成分体内药动学研究 |
投稿时间:2021-11-02 修订日期:2022-03-27 点此下载全文 |
引用本文:戴媛媛,马明华,徐晓红,汪晓河,张若曦,徐智儒,年华.LC-MS/MS法测定大鼠血浆中夏枯草消瘤合剂有效成分体内药动学研究[J].药学实践杂志,2023,41(6):358~365 |
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基金项目:上海市中药专家传承工作室建设项目(2020ZYGZS-002);上海市卫生健康委员会中医药科研项目(2020YP001) |
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中文摘要:目的 建立LC-MS/MS测定大鼠血浆样品中夏枯草消瘤合剂有效成分浓度的方法,并进行药动学研究。方法 采用C18色谱柱正离子模式下流动相为甲醇-水(0.1% 甲酸)体系,梯度洗脱,流速为 0.3 ml/min。负离子模式下流动相为乙腈-水(0.1% 甲酸)体系,梯度洗脱,流速为 0.4 ml/min。分别对正离子模式下咖啡酸、迷迭香酸、丁香酸、芦丁及负离子模式下白术内酯Ⅱ、白术内酯Ⅲ进行测定。 正常大鼠灌胃给予夏枯草消瘤合剂7.8 ml/kg,给药后在不同的时间点眼眶取血,采用经过验证的LC-MS/MS法测定血药浓度并采用 DAS2.0 软件的非房室模型计算大鼠给药后的药动学参数。结果 夏枯草消瘤合剂药效成分咖啡酸等的药动学参数属于非房室模型,夏枯草消瘤合剂大鼠给药后体内咖啡酸、迷迭香酸、丁香酸及白术内酯Ⅲ等4种主要抗癌活性成分与文献报道单体给药后药动学特征相比,均存在明显差异。结论 本研究建立的UPLC-MS/MS法快速、灵敏、准确,适用于测定大鼠血浆中夏枯草消瘤合剂主要活性成分,为其主要抗癌活性物质研究提供科学依据。 |
中文关键词:药动学 夏枯草消瘤合剂 液相色谱-串联质谱分析仪 |
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In vivo pharmacokinetic study on determination of effective components in Xiakucao Xiaoliu mixture in Normal Rat Plasma By LC-MS/MS |
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Abstract:Objective To establish a method and study the pharmacokinetics for concentration determination of effective components in Xiakucao Xiaoliu mixture in Normal Rat Plasma By LC-MS/MS. Methods The mobile phase was methanol-water (0.1% formic acid) system under the positive ion mode of C18 chromatographic column, gradient elution was adopted, and the flow rate was 0.3 ml/min. In the negative ion mode, the mobile phase was acetonitrile-water (0.1% formic acid) system, gradient elution, with a flow rate of 0.4 ml/min. Caffeic acid, rosmarinic acid, syringic acid, rutin in positive ion mode and Atractylodes lactone II and Atractylodes lactone III in negative ion mode were respectively determined. Normal rats were intragastrically given Xiakucao Xiaoliu Mixture 7.8 ml/kg, and blood was taken from the orbit at different time points after the administration. The blood concentration was determined by the validated LC-MS/MS method and the non-standard DAS2.0 software was used. The pharmacokinetic parameters of rats after administration were calculated by the compartment model. Results The pharmacokinetic parameters belonged to non atrioventricular model. The pharmacokinetic characteristics of the four main anti-cancer active ingredients of Caffeic acid, Rosmarinic acid, Syringic acid and Atractylodes Ⅲ in rats after administration of Xiakucao Xiaoliu Mixture were significantly different from those reported in the literature after the administration of monomers. Conclusion The established method was simple, accurate and sensitive, which could be suitable for the content determination of effective components in Xiakucao Xiaoliu mixture in Normal Rat Plasma, which would be a valuable information for the study on main anticancer active substances. |
keywords:Pharmacokinetics Xiakucao Xiaoliu mixture LC-MS |
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