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超高效液相色谱-串联质谱法同时定量大鼠血浆中多种成分及黄芪汤口服给药后的药代动力学研究

Simultaneous quantification of multiple components in rat plasma by UPLC-MS/MS and pharmacokinetic study after oral administration of Huangqi decoction.

作者信息

Zeng Jia-Kai, Li Yuan-Yuan, Wang Tian-Ming, Zhong Jie, Wu Jia-Sheng, Liu Ping, Zhang Hua, Ma Yue-Ming

机构信息

Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Biomed Chromatogr. 2018 May;32(5):e4178. doi: 10.1002/bmc.4178. Epub 2018 Jan 18.

Abstract

A rapid, sensitive and accurate UPLC-MS/MS method was developed for the simultaneous quantification of components of Huangqi decoction (HQD), such as calycosin-7-O-β-d-glucoside, calycosin-glucuronide, liquiritin, formononetin-glucuronide, isoliquiritin, liquiritigenin, ononin, calycosin, isoliquiritigenin, formononetin, glycyrrhizic acid, astragaloside IV, cycloastragenol, and glycyrrhetinic acid, in rat plasma. After plasma samples were extracted by protein precipitation, chromatographic separation was performed with a C column, using a gradient of methanol and 0.05% acetic acid containing 4mm ammonium acetate as the mobile phase. Multiple reaction monitoring scanning was performed to quantify the analytes, and the electrospray ion source polarity was switched between positive and negative modes in a single run of 10 min. Method validation showed that specificity, linearity, accuracy, precision, extraction recovery, matrix effect and stability for 14 components met the requirements for their quantitation in biological samples. The established method was successfully applied to the pharmacokinetic study of multiple components in rats after intragastric administration of HQD. The results clarified the pharmacokinetic characteristics of multiple components found in HQD. This research provides useful information for understanding the relation between the chemical components of HQD and their therapeutic effects.

摘要

建立了一种快速、灵敏、准确的超高效液相色谱-串联质谱(UPLC-MS/MS)方法,用于同时定量大鼠血浆中黄芪汤(HQD)的多种成分,如毛蕊异黄酮-7-O-β-D-葡萄糖苷、毛蕊异黄酮葡萄糖醛酸苷、甘草苷、芒柄花素葡萄糖醛酸苷、异甘草苷、甘草素、鹰嘴豆芽素A、毛蕊异黄酮、异甘草素、芒柄花素、甘草酸、黄芪甲苷、环黄芪醇和甘草次酸。血浆样品经蛋白沉淀法提取后,采用C柱进行色谱分离,以甲醇和含4mM醋酸铵的0.05%醋酸为流动相进行梯度洗脱。采用多反应监测扫描对分析物进行定量,在10分钟的单次运行中,电喷雾离子源极性在正、负模式之间切换。方法学验证表明,14种成分的特异性、线性、准确性、精密度、提取回收率、基质效应和稳定性均符合生物样品定量分析的要求。所建立的方法成功应用于大鼠灌胃给予HQD后多种成分的药代动力学研究。结果阐明了HQD中多种成分的药代动力学特征。本研究为理解HQD化学成分与其治疗效果之间的关系提供了有用信息。

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