丹参酮Ⅱ_A自微乳制剂在大鼠体内血药浓度测定

Determination of Tanshinone Ⅱ_A in the Self-Microemulsifying Preparation in Rat Plasma

目的建立大鼠血浆中丹参酮ⅡA浓度的测定方法,考察丹参酮ⅡA自微乳制剂的药动学特征。方法采用乙腈沉淀蛋白进行血浆预处理,以HPLC测定给药后大鼠血浆中丹参酮ⅡA的浓度。色谱柱为Kromasil C18柱（250 mm×4.6 mm,5.0μm）,流动相为乙腈-0.01 mol.L-1枸橼酸水溶液（80∶20）,流速1.0 mL.min^-1,检测波长：270 nm,柱温25℃。比较丹参酮ⅡA自微乳制剂组和混悬液组大鼠血药浓度曲线的差异。结果丹参酮ⅡA在0.102－8.2 mg.L^-1内线性关系良好（r=0.998 6）,绝对回收率为77.5%-85.6%,相对回收率为88.3%-96.8%,日内和日间精密度RSD均小于15%。丹参酮ⅡA自微乳制剂比丹参酮ⅡA混悬液的AUC值高约2.5倍。结论本法可以准确、灵敏地测定大鼠血浆中丹参酮ⅡA的浓度。将丹参酮ⅡA制成自微乳制剂,能提高其生物利用度。

OBJECTIVE To establish a method for the determination of tanshinone ⅡA in rat plasma and investigate pharmcokinetic characteristics of tanshinone ⅡA self-microemulsifying preparation（TSP）.METHODS Protein precipitation method with acetonitrile was applied to purify plasma samples before analysis.The concentration of tanshinone ⅡA in rat plasma was detected by HPLC using Kromasil C18 column（250 mm×4.6 mm,5.0 μm）.The mobile phase was consisted of acetonitrile and 0.01 mol.L^-1 citric acid solution（80∶20）.The flow rate was 1 mL.min^-1 and the column temperature was 25 ℃.The detection wavelength was 270 nm.The pharmacokinetic profiles of tanshinone ⅡA between self-emusifying and suspension were compared by oral administration.RESULTS The standard curve was linear over the range of 0.102-8.2 mg.L^-1（r=0.998 6）.The absolute recovery was 77.5% to 85.6%,and the assay recovery was 88.3% to 96.8%.The intra-and inter-day precision RSD were less than 15%.The AUC after TSP administration was approximately 2.5-fold compared with that of the suspension.CONCLUSION The method is accurate and sensitive for the determination of tanshinone ⅡA in rat plasma.Bioavailability of tanshinone ⅡA was improved by self-microemulfying.