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一种使用液相色谱/串联质谱法测定大鼠血浆中丹酚酸A的灵敏方法。

A sensitive method for determination of salvianolic acid A in rat plasma using liquid chromatography/tandem mass spectrometry.

作者信息

Pei Lixia, Bao Yuanwu, Wang Haidi, Yang Fan, Xu Bei, Wang Shoubao, Yang Xiuying, Du Guanhua

机构信息

Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.

出版信息

Biomed Chromatogr. 2008 Jul;22(7):786-94. doi: 10.1002/bmc.1043.

DOI:10.1002/bmc.1043
PMID:18506911
Abstract

Salvianolic acid A (SAA), a major effective constituent of Salvia miltiorrhizas, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated for SAA in rat plasma, which was further applied to assess the pharmacokinetics of SAA in rats receiving a single oral dose of SAA. The method used liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode with chloramphenicol as the internal standard. A simple liquid-liquid extraction based on ethyl acetate was employed. The combination of a simple sample cleanup and short chromatographic run time (3 min) increased the throughput of the method substantially. The method was validated over the range 1.4-1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1.4 ng/mL for SAA in plasma. Intra- and inter-day accuracies for SAA were 95-113 and 98-107%, and the inter-day precision was less than 12%. This method is more sensitive and faster than previous methods. After a single oral dose of 100 mg/kg of SAA, the mean peak plasma concentration (Cmax) of SAA was 318 ng/mL at 0.5 h, the area under the plasma concentration-time curve (AUC0-12 h) was 698 +/- 129 ng.h/mL, and the elimination half-life (T1/2) was 3.29 h.

摘要

丹参酚酸A(SAA)是丹参的主要有效成分,在传统中药中广泛应用。建立并验证了一种灵敏快速的大鼠血浆中SAA分析方法,并将其进一步应用于评估单次口服SAA的大鼠体内SAA的药代动力学。该方法采用液相色谱串联质谱的多反应监测模式,以氯霉素为内标。采用基于乙酸乙酯的简单液液萃取法。简单的样品净化与较短的色谱运行时间(3分钟)相结合,大大提高了该方法的通量。该方法在1.4 - 1000 ng/mL范围内进行了验证,相关系数>0.99。血浆中SAA的定量下限为1.4 ng/mL。SAA的日内和日间准确度分别为95 - 113%和98 - 107%,日间精密度小于12%。该方法比以前的方法更灵敏、更快。单次口服10​​0 mg/kg的SAA后,SAA的平均血浆峰浓度(Cmax)在0.5小时时为318 ng/mL,血浆浓度-时间曲线下面积(AUC0 - 12 h)为698 +/- 129 ng.h/mL,消除半衰期(T1/2)为3.29小时。

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