紫杉醇注射液在小鼠体内的药代动力学及组织分布

Study on pharmacokinetics and tissue distribution of paclitaxel injection in mice

目的：建立血清中紫杉醇的分析测定方法,进行紫杉醇注射液在小鼠体内的药代动力学研究。方法：采用固相萃取方法进行血清样品预处理。色谱柱为Intertex C18（150 mm×4.6 mm,5μm）,流动相为磷酸水溶液（pH3.0）-乙腈（50∶50）,流速为1 mL.min-1,检测波长为227 nm。结果：紫杉醇在血清和组织中的浓度范围分别为0.39~100.00μg.mL-1和0.39~25.00μg.mL-1,准确度均在85%~115%,稳定性RSD均小于15%,小鼠静脉注射紫杉醇注射液后在小鼠体内代谢符合三房室模型（W=1/C2）。结论：本方法简便快捷,灵敏准确,本文建立的紫杉醇血药浓度测定方法和紫杉醇注射液在小鼠体内的药代动力学参数,为紫杉醇其他制剂的研究提供参考。

Objective：To establish an RP-HPLC method for the determination concentration of paclitaxel in serum and tissues in mice.Methods：The Intertex C18 column（150 mm×4.6 mm,5 μm） was used and the detection was carried out at the wavelength of 227 nm with UV detector.Diazepam and taxotere were used as the internal standard,the solid phase extraction（SPE） was used to extract the sample,the mobile phase consisted of phosphoric acid-acetonitrile（50∶50） delivered at a flow rate of 1 mL·min-1.Results：The linear range of paclitaxel in serum and tissue were 0.39-100.00 μg·mL-1 and 0.39-25.00 μg·mL-1,the accuracy were ranged from 85% to 115%,the RSD value of stability were all less than 15%.We found from the results that the concentration-time curve of paclitaxel injection in mice serum could be fitted to three-compartment model（W=1/C2）.Conclusion：The method is simple,sensitive and accurate,these finding can provide reference during pharmacokinetics investigations for the other preparations of paclitaxel.