目的 建立快速、简单测定小鼠血浆和组织中盐酸川芎嗪浓度的HPLC方法,研究丹参川芎嗪注射液和盐酸川芎嗪原料药在健康昆明小鼠体内的药动学特征和组织分布。方法 168只小鼠,雌雄各半,分为4组,单次尾静脉注射,分别给予低、中、高剂量的丹参川芎嗪注射液和对照盐酸川芎嗪原料药,测定小鼠体内血浆及组织中的药物浓度。结果 本方法血浆中盐酸川芎嗪线性范围为0.121 8~243.7 μg·mL-1(r=0.997 5),组织中盐酸川芎嗪线性范围为0.1218~60.92 μg·mL-1(r=1.000);日内及日间精密度RSD均小于9%。小鼠不同剂量静脉给予丹参川芎嗪注射液后,盐酸川芎嗪可快速分布于各组织,丹参川芎嗪注射液中盐酸川芎嗪在各组织中的浓度均高于对照组,盐酸川芎嗪在体内的处置均符合一室模型。结论 本实验建立的HPLC方法专属性强,简便,快速,准确;盐酸川芎嗪在体内呈现非线性动力学,吸收迅速,分布广泛。
Abstract
OBJECTIVE To set up a rapid and simple HPLC method for the determination of ligustrazine hydrochloride in plasma and tissues in mice, and study the pharmacokinetic characteristics and tissue distribution in healthy Kunming mice after intravenous injection of Salviae miltiorrhiza ligustrazine hydrochloride injection and ligustrazine hydrochloride. METHODS The 168 Mice, with half males and females, were divided into four groups, and injected low, medium and high doses of salvia miltiorrhiza ligustrazine hydrochloride injection or ligustrazline hydrochloride by caudal vein, drug concentrations in plasma and tissues were determined by HPLC. RESULTS The linear ranges of ligustrazine hydrochloride in plasma and tissues were 0.121 8-243.7 μg·mL-1(r=0.997 5) and 0.121 8-60.92 μg·mL-1(r=1.000), respectively. The intra-day and inter-day RSD were less than 9%. After intravenous injection different doses of Salviae miltiorrhiza ligustrazine hydrochloride injection in mice, ligustrazine hydrochloride can rapidly distribute in each organ and the concentrations in the experiment groups were higher than that of the control group, the disposal of ligustrazine hydrochloride in mice was fitted to one-compartment model. CONCULSION The established HPLC method is specific, simple, rapid and accurate; ligustrazine hydrochloride presents non-linear dynamic characteristics in mice, and it is absorbed quickly and distributed widely.
关键词
丹参川芎嗪注射液 /
盐酸川芎嗪 /
高效液相色谱法 /
药动学 /
组织分布
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Key words
Salvia miltiorrhiza ligustrazine hydrochloride injection /
ligustrazine hydrochloride /
HPLC /
pharmacokinetics /
tissue distribution
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中图分类号：
R969.1
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参考文献
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