Pharmacy Department, the Fourth Affiliated Hospital of China Medical University, Chongshan Eastern, Huanggu District, Shenyang, P R China.
J Sep Sci. 2012 Jun;35(12):1539-46. doi: 10.1002/jssc.201200039. Epub 2012 Jun 18.
A simple and efficient method based on cloud-point extraction combined with high-performance liquid chromatography was developed and validated for the determination of larotaxel in rat plasma. Nonionic surfactant Triton X-114 was chosen as the extraction solvent. Variable parameters affecting the cloud-point extraction efficiency, for example the nature and concentration of surfactant, NaOH concentration, incubation temperature, and time were evaluated and optimized. Chromatographic separation was accomplished on a Diamonsil C(18) column (150 mm × 4.6 mm, 5 μm) using a mobile phase consisting of acetonitrile and 0.1% phosphoric acid with pH 4.0 (60:40, v/v). The calibration curve showed good linearity over the range of 0.05-10 μg/mL. Under the optimum conditions, the method was shown to be reproducible and reliable with intraday precision below 5.7%, interday precision below 7.2%, accuracy within ±3.5%, and mean extraction recovery of 91.8-94.2%. The validated method was successfully applied to the pharmacokinetic study of larotaxel in rat plasma after a single intravenous administration of larotaxel injection and larotaxel-loaded liposome, respectively. The results indicated that the larotaxel-loaded liposome led to significant differences in pharmacokinetic profile.
建立并验证了一种基于浊点萃取结合高效液相色谱法测定大鼠血浆中拉罗他赛浓度的方法。选用非离子表面活性剂 Triton X-114 作为萃取溶剂。考察并优化了影响浊点萃取效率的各种参数，如表面活性剂的种类与浓度、NaOH 浓度、孵育温度和时间。采用 Diamonsil C18（150mm×4.6mm，5μm）色谱柱，以乙腈-0.1%磷酸（pH4.0）（60:40，v/v）为流动相进行梯度洗脱，实现了色谱分离。在 0.05-10μg/mL 范围内，该方法的校准曲线具有良好的线性关系。在优化条件下，日内精密度低于 5.7%，日间精密度低于 7.2%，准确度在±3.5%以内，平均提取回收率为 91.8%-94.2%。该方法已成功应用于单静脉给予拉罗他赛注射液和拉罗他赛脂质体后大鼠血浆中的药代动力学研究。结果表明，拉罗他赛脂质体使药代动力学特征产生显著差异。
