互为内标法测定紫杉醇和多西紫杉醇血浆药物浓度及临床应用

Determination of Paclitaxel and Docetaxel in Plasma by Crossing Internal Standard Method and its Clinical Application

目的：建立高效液相色谱（HPLC）法测定人血浆中紫杉醇、多西紫杉醇浓度为临床个体化给药方案、疗效及不良反应评价提供实验依据。方法：紫杉醇和多西紫杉醇互为内标,血浆样品采用乙腈提取法,以Dik MA Diamonsil C18反相色谱柱分离样品,流动相为乙腈∶水（55∶45）,检测波长为227 nm,流速为1.2 ml·min-1,柱温为25℃。结果：紫杉醇和多西紫杉醇血药浓度在0.078-10.0 mg·L-1范围内线性关系良好;最低定量下限为0.039 mg·L-1;平均方法回收率分别为99.85%和100.35%;日内、日间相对标准差均低于5%;短期稳定性、长期稳定性和反复冻融稳定性相对标准差均低于10%。紫杉醇临床样本血浆药物浓度监测结果范围为0.18-6.16 mg·L-1,临床监测结果存在明显个体差异。结论：紫杉醇和多西紫杉醇血浆药物浓度差异明显,进行两药治疗药物监测十分必要。本方法灵敏、准确、便捷、快速,适用于紫杉醇和多西紫杉醇的临床常规治疗药物监测及药动学研究。

Objective：To establish an HPLC method for the determination of paclitaxel and docetaxel in plasma to provide refer-ence for the individualized treatment regimen and the evaluation of curative effect and adverse reactions. Methods：Paclitaxel and do-cetaxel were used as the internal standard for each other. The samples were precipitated by acetonitrile and separated on a DikMA Dia-monsil C18 column with a mixture of acetonitrile-water （55： 45） as the mobile phase. The flow rate was 1. 2 ml·min-1 . The column temperature was set at 25℃. Paclitaxel and docetaxel were detected by UV-detection （λ= 227 nm）. Results： A linearity was ob-tained within the range of 0. 078-10. 0 mg·L-1 for paclitaxel and docetaxel. The limit of quantitation was 0. 039 mg·L-1 . The aver-age recovery of paclitaxel and docetaxel was 99. 85% and 100. 35%, respectively. The inter- and intra-day RSD were both less than 5% and the RSD for freeze-thaw stability was below 10%. The plasma concentration of paclitaxel in clinical samples was within the range of 0. 18-6. 16 mg·L-1 and obvious individual difference was shown. Conclusion：Therapeutic drug monitoring is very important due to the obvious differences in plasma concentration of paclitaxel and docetaxel. The established method is sensitive, accurate, con-venient and rapid in r the therapeutic drug monitoring, and is useful for the adverse drug reactions monitoring and pharmacokinetic study.