UPLC-MS/MS法测定黄芪桂枝五物汤在大鼠血浆中两种活性成分及药代动力学研究

doi:10.5246/jcps.2018.04.027

摘要/Abstract

摘要：

建立快速、灵敏、高选择性的超高效液相色谱-质谱联用(UPLC-MS/MS)方法同时检测芍药苷和黄芪甲苷的含量,并应用该方法对芍药苷和黄芪甲苷在大鼠血浆的药代动力学进行了研究。采用简单的一步去蛋白的处理方法来制备血浆样品, 内标为克拉霉素。采用CAPCELL CORE ADME C₁₈色谱柱, 流动相由溶液A(含0.1%甲酸的水)和溶液B(乙腈)组成, 流速为0.3 mL/min。采用电喷雾正离子多反应监测(MRM)模式检测。芍药苷、黄芪甲苷分别在0.01–5.00 μg/mL、0.0001–0.05 μg/mL范围内呈良好的线性关系; 准确度(RE)在–3.5%至6.3%的范围内; 日内和日间精度(RSD)均在14.2%以内;提取回收率均在78.9%以上。通过该方法对黄芪桂枝五物汤大鼠体内两种活性成分的药代动力学进行了研究, 填补黄芪桂枝五物汤药代动力学研究领域的空白。

关键词: 黄芪桂枝五物汤, 药代动力学, 大鼠血浆, UPLC-MS/MS

Abstract:

A rapid, sensitive and selective UPLC-MS/MS method was developed to determine paeoniflorin and astragaloside IV. This method was validated via a pharmacokinetic study using rat plasma. The internal standard was clarithromycin. A simple one-step deproteinization procedure was used to prepare plasma samples. Separation was achieved on a CAPCELL CORE ADME C₁₈ column with a gradient mobile phase consisting of solution A (water containing 0.1% formic acid) and solution B (acetonitrile) at a flow rate of 0.3 mL/min. Multiple reaction monitoring (MRM) was used with an electrospray ionization source (ESI) in positive mode. A good linear response was observed within the ranges of 0.01 to 5.00 μg/mL for paeoniflorin and 0.0001 to 0.05 μg/mL for astragaloside IV. The accuracy (RE) was within the range of –3.5% to 6.3%, and the intra- and inter-day precisions (RSD) were within 14.2%. The extraction recoveries were all above 78.9%. The pharmacokinetic study of the two analytes in rats after oral administration of Huangqi Guizhi Wuwu Decoction (HGWD) was successfully completed through this method. The method developed in this study will fill a gap in pharmacokinetic studies of HGWD.

Key words: Huangqi Guizhi Wuwu Decoction, Pharmacokinetics, Rat plasma, UPLC-MS/MS

中图分类号:

R969.1

Supporting:

常馨予, 郭桂明, 范峥, 王宏蕾, 刘洋, 韩丽娟. UPLC-MS/MS法测定黄芪桂枝五物汤在大鼠血浆中两种活性成分及药代动力学研究[J]. 中国药学(英文版), 2018, 27(4): 263-272.

Xinyu Chang, Guiming Guo, Zheng Fan, Honglei Wang, Yang Liu, Lijuan Han. Simultaneous determination of two bioactive components of Huangqi Guizhi Wuwu Decoction in rat plasma using UPLC-MS/MS and its application to a pharmacokinetic study[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(4): 263-272.

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