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目的:建立LC-MS法测定大鼠血浆洋川芎内酯I(senkyunolide Ⅰ,SI)的浓度,比较活络效灵丹加减方(HLXL)和川芎单味药材提取物中SI在大鼠体内的药代动力学参数有无显著性变化,评价HLXL提取物中其他成分对SI药动学的影响。方法:将12只大鼠随机分成2组,按含SI计4.53 mg.kg-1分别灌胃给予HLXL提取物和川芎提取物,不同时间点采血后进行LC-MS分析,测定血浆SI浓度,采用DAS 2.0软件对主要药动学参数进行计算,并用SPSS 16.0软件对其进行独立样本t-检验和非参数t-检验分析。结果:SI在6.750～675.0μg.L-1线性关系良好,最低检测限为6.750μg.L-1。大鼠灌胃HLXL提取物和川芎提取物的药-时曲线均符合二房室模型,测得SI的Cmax,AUC0-24 h和CL有显著性差异,其他参数均无显著性差异。结论:该实验建立的LC-MS测定法专属、准确、灵敏,适用于HLXL提取物和川芎提取物中SI的药动学研究。实验结果表明,HLXL中其他药材对SI的吸收有较大影响。
OBJECTIVE: To establish a method for determining the concentration of senkyunolide I (SI) in rat plasma by LC-MS. To compare the effect of active ingredient Lingxiao Dan addition and decoction (HLXL) and single extract of Chuanxiong rhizome on the content of SI in rats Pharmacokinetic parameters with or without significant changes in the evaluation of HLXL extract other components of the SI pharmacokinetics. Methods: Twelve rats were randomly divided into two groups. The extract of HLXL and extract of Chuanxiong Rhizoma were extracted by intragastric administration of 4.53 mg.kg-1 SI. The blood samples were collected at different time points and analyzed by LC-MS. The main pharmacokinetic parameters were calculated by DAS 2.0 software, and independent samples t-test and non-parametric t-test were used to analyze the parameters with SPSS 16.0 software. Results: The linearity of SI was 6.750 ~ 675.0μg.L-1 with the lowest detection limit of 6.750μg.L-1. The drug-time curves of HLXL extract and Chuanxiong extract in rats were in accordance with the two-compartment model. The Cmax, AUC0-24 h and CL of SI were significantly different between the two groups. Other parameters had no significant difference. Conclusion: The LC-MS assay established in this experiment is specific, accurate and sensitive and suitable for pharmacokinetic studies of SI in HLXL extract and Chuanxiong extract. The experimental results show that, HLXL other herbs have a greater impact on SI absorption.