丹参脂溶性提取物隐丹参酮和丹参酮ⅡA在大鼠体内的药动学研究

Study on pharmacokinetics of cryptotanshinone and tanshinone ⅡA from the liposoluble extract of Salvia miltiorrhiza in rats

目的：建立同时测定大鼠血浆中隐丹参酮和丹参酮ⅡA浓度的反相高效液相色谱法,并对大鼠口服丹参脂溶性提取物后的2种丹参酮成分进行药动学研究。方法大鼠分别灌胃丹参脂溶性提取物混悬液（隐丹参酮和丹参酮ⅡA的灌胃剂量分别为38.4 mg·kg-1和70.1 mg·kg-1）后,眼眶静脉丛取血,经乙腈-乙酸乙酯（体积比1∶4）液-液萃取后采用HPLC法测定不同时间点的血药浓度,并用3P97软件计算药动学参数。结果隐丹参酮在0.05-5μg·mL-1内线性良好,方法回收率为99.7%~106．6%；丹参酮ⅡA在0.02-5μg·mL-1内线性良好,方法回收率为93.3%-102.5%。大鼠体内隐丹参酮和丹参酮ⅡA的t1/2（ka）分别为0.924、0.993 h,t1/2（ke）分别为2.632、2.126 h,Cmax分别为0.277、0．173μg·mL-1,AUC0-t分别为1.855、1.034μg·h·mL-1,CL/F（s）分别为20.700、67.763 mL·h-1·mg-1。结论建立的方法快速、简便、准确,可用于丹参脂溶性提取物中隐丹参酮和丹参酮ⅡA血浆样品的含量测定及药动学研究。

Objective To develop a reversed phase high-performance liquid chromatography for simultaneous determination cryptotanshinone and tanshinone ⅡA in rat plasma and to study on pharmacokinetics of the two tanshiones. Method The rats was administered the extract of Salvia miltiorrhiza （ 38. 4 mg · kg-1 cryptotanshinone and 70.1 mg·kg-1 tanshinone ⅡA）, and the blood samples were collected from eye ophthalmic vein jungle venous plexus. After liquid liquid exatraction with acetonitrile-ethyl acetate, plasma concentrations of cryptotanshinone and tanshinone ⅡA were determined by HPLC. The 3P97 software package was used to calculate the pharmacokinetic parameters. Result A good linear relationship of cryptotanshinone was obtained from 0.05 to 5μg·mL-1 ,and the method recoveries were all from 99.7%-106.6%. A good linear relationship of tanshinone ⅡA was obtained from 0.02 to 5 μg·mL-1,and the method recoveries were all from 93.3%-102.5%. The pharmacokinetic parameters of cryptotanshinone and tanshinoneⅡA were as follows：t1/2（ka） was 0.924,0.993 h,t1/2（ke） was 2.632,2.126 h,Cmax was 0. 277,0.173μg·mL-1,AUC0-t was 1.855,1.034 μg·h·mL-1,CL/F（s） was 20.700,67.763 mL·h-1·mg-1. Conclusion The analysis method is rapid,simple and sensitive enough to be applied in the detection and pharmacokinetic study of cryptotanshinone and tanshinone ⅡA.