丹参川芎嗪注射液中丹参素及丹酚酸A在大鼠体内药动学研究

Pharmacokinetics Study of Danshensu and Salvianolic Acid A in Salviae Miltiorrhiza and Ligustrazine Injection in Rats

本研究用建立并验证的LC-MS/MS方法测定大鼠尾静脉给药后血浆中丹参素、丹酚酸A浓度,比较丹参川芎嗪注射液和单体组的丹参素、丹酚酸A在健康大鼠体内的药动学差异。所建立的LC-MS/MS法方法学验证结果均符合要求。实验结果表明,相同剂量下丹参川芎嗪注射液组中丹参素的C max、AUC 0-t和MRT 0-t约为单体组的1.7~1.8倍,丹酚酸A的C max、AUC 0-t和MRT 0-t约为单体组的1.5倍。丹参川芎嗪注射液中的丹参素、丹酚酸A在大鼠体内暴露量明显高于单独给药组,且消除更慢。本实验从药动学的角度研究表明丹参川芎嗪注射液可以增加单体成分丹参素、丹酚酸A的体内暴露量。

In this study,the established and validated LC-MS/MS method is used to determine the plasma concentration of Danshensu and salvianolic acid A in rats after tail vein administration,and the pharmacokinetic differences of Danshensu and salvianolic acid A in healthy rats between Salviae Miltiorrhiza and Ligustrazine Injection(SMLI)and monomer drug group are compared at the same dose.The validation results of the LC-MS/MS method meet the requirements of the guideline.The results show that at the same dose,the C max,AUC 0-t and MRT 0-t of Danshensin in SMLI group are about 1.7-1.8 times higher than those of the monomer group,and the C max,AUC 0-t and MRT 0-t of salvianolic acid A are about 1.5 times higher than those of the monomer group.The exposure of Danshensu and salvianolic acid A in rats of SMLI group is significantly higher than that in the monomer group,and the elimination is slower than monomer drug group.From the perspective of pharmacokinetics,this study indicates that SMLI can increase the exposure of Danshensu and salvianolic acid A monomer components in vivo.