马建军 陈金凤 嗓晓静

摘要：目的： 建立高效液相色谱法（HPLC）测定大鼠肝组织匀浆中多西紫杉醇的方法，考察多西紫杉醇大鼠尾静脉给药后肝组织中的浓度。方法： 以紫杉醇为内标，大鼠肝组织匀浆样品中多西紫杉醇经萃取后采用SymmetryShield RP18柱（5μm，250×4.6mm）色谱分析柱 ，流动相为乙腈-水（50：50）流速：1.0 ml/min，检测波长为231nm，进样量 20u L。大鼠尾静脉注射给予多西紫杉醇制剂，剂量为75mg/m2。经不同时间点解剖动物，用所建立的 HPLC法测定其肝组织中药物浓度。结果：紫杉醇和多西紫杉醇的保留时间分别是13.7 min 和11.4 min ， 肝组织样品中多西紫杉醇在0.986～49.3mg/L浓度范围内与峰面积之间线性关系良好 ，回归方程为Y = 1.587213X -5.959293e-002，绝对回收率和相对回收率分别为85%～100%、80% ～115%，日内 RSD为12.81%、7.17%、3.11% ，日间RSD为10.61% 、3.5%、9.38% ， 且稳定性良好。实测得多西紫杉醇在大鼠肝组织中的浓度为177.7～3904.3μg/g。结论：本试验建立的方法简便灵敏 ，干扰小 ，重复性好 ，可实际应用于多西紫杉醇在大鼠肝组织中的测定 ，并作为评价多西紫杉醇在靶组织分布的方法学依据。

关键词：多西紫杉醇； 肝组织； 高效液相色谱法

Abstract：Objective to establish HPLC method for determination of docetaxel in rat liver tissue，and to investigation the docetaxel concentration in rat liver tissue after intravenous administration .METHODS Taxol was used as internal standard. The docetaxel was extracted for two times determined through SymmetryShield RP18 column （5μm，250*4.6mn） chromatography column .The mobile phase consisted of water-acetonitrile （50：50） with the flow rates of 1.0ml/min.The detection wavelength was 231nm. Docetaxel was intravenously administrated to rat at a single dosage of 75mg/㎡.The rat were dissectted at different time points and docetaxel of hepatic tissue was determined by HPLC.RESULTS In this system，the retention times of Taxol and docetaxel were 13.7 min and 11.4min ，respectively. Docetaxel concentration presented a good linear range of 0.986～49.3mg/L.The linear regression equation Y = 1.587213X -5.959293e-002.Absolute recovery and relative recoveries were 85%to100%，80%to115%.Within-day RSDs were 12.81%、7.17%、3.11%，and the between-day RSDs were 10.61%、3. 5%、9.38%.The concentration of Docetaxel in rat liver tissue were177.7～3904.3μg/g.CONCLUSION The method is reliable ，convenient and efficient and can be applied to the determination of docetaxel concentration of rat hepatic tissue in the tissue distribution research of docetaxel.

KEYWORDS： docetaxel； hepatic tissue； HPLC

多西紫杉醇 （docetaxel ，Doc ，又名多西他赛） 是新一代紫杉烷类抗肿瘤药物。商品名为 taxotere （泰索帝） [1]。由于多西紫杉醇以t-丁氧羰基取代了紫杉醇中的苯甲酸基团，因而水溶性略大于紫杉醇。市售制剂泰索帝（Taxotere）采用Tween80增溶、乙醇助溶，将其制成一个注射剂浓缩液和一个溶剂的两瓶装。其中注射剂浓缩液为含有主药的Tween80溶液，溶剂为13%（w/w）的注射乙醇，使用时先将溶剂加入浓缩液中混合均匀，临用前再用生理盐水或5%葡萄糖注射液稀释后使用。……