丹参酮ⅡA自微乳制剂在大鼠体内血药浓度测定

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

关键词:  丹参酮Ⅱ_A  自微乳  血药浓度

Key words:  tanshinone II_A  self-microemulsion  plasma concentration

摘要:

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Ⅱ_A的浓度。色谱柱为Kromasil C₁₈柱(250 mm×4.6 mm，5.0 μm)，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Ⅱ_A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Ⅱ_A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Ⅱ_A自微乳制剂比丹参酮Ⅱ_A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Ⅱ_A的浓度。将丹参酮Ⅱ_A制成自微乳制剂，能提高其生物利用度。

Abstract:

OBJECTIVE To establish a method for the determination of tanshinone Ⅱ_A in rat plasma and investigate pharmcokinetic characteristics of tanshinone Ⅱ_A self-microemulsifying preparation (TSP). METHODS Protein precipitation method with acetonitrile was applied to purify plasma samples before analysis. The concentration of tanshinone Ⅱ_A in rat plasma was detected by HPLC using Kromasil C₁₈ column(250 mm×4.6 mm, 5.0 mm). 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 Ⅱ_A 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 Ⅱ_A in rat plasma. Bioavailability of tanshinone Ⅱ_A was improved by self-microemulfying.