液相色谱-质谱联用法考察多西他赛脂质体犬体内药动学

Pharmacokinetics of docetaxel liposomes injection in Beagle dogs by liquid chromatography-mass spectrometry

目的:研究多西他赛脂质体Beagle犬体内药动学。方法:采用单剂量双周期自身交叉设计, Beagle犬前肢皮下头静脉分别滴注多西他赛脂质体和多西他赛注射液(参比制剂),建立液相色谱-质谱联用(LC-MS)法测定不同时间血浆中多西他赛浓度。结果:多西他赛在0．5～2 000μg·L^(-1)范围内线性关系良好(r＞0．99),提取回收率大于90%,日内、日间精密度RSD＜15%。多西他赛脂质体和多西他赛注射液,CL分别为(11±s 6)和(25±6)L·h^(-1),AUC_(0～∞)分别为(2630±1115)和(1148±310)μg L^(-1)·h,MRT分别为(4．1±2．0)和(2．7±1．3)h,且2种制剂的CL、AUC_(0～∞)和MRT均具有显著或非常显著差异。结论:本方法灵敏度高,准确、可靠。与多西他赛注射液相比,多西他赛脂质体具有一定的缓释和长循环特征。

AIM： To study the pharmacokinetics of docetaxel liposomes injection in Beagle dogs. METHODS： In a two-period cross-over design, a liquid chromatography-mass spectrometric （LC-MS） assay has been developed for the determination of docetaxel in plasma of dogs administered docetaxel liposomes injection and reference preparation via left anterior cardinal vein, respectively. RESULTES： The standard curve was linear over the concentration range of 0.5-2 000 μg·L^-1 （r 〉 0.99） . The extraction recovery was 〉 90 %. The intraday and interday precisions were 〈 15 %. The main pharmacokinetic parameters of docetaxel liposomes and reference preparation were as follows： CL were （11 ± s 6） and （25 ± 6） L·h^-1, AUC0-∞ were （2 630 ±1 115） and （1 148 ± 310） μg·L^-1·h, MRT were （4.1 ± 2.0） and （2.7 ± 1.3） h, respectively. The difference of CL, A UC0-∞ and MRT were significant between two preparations. CONCLUSION： The LC-MS method is high sensitivity, accuracy and reliability for the determination of docetaxel in plasma. Compared with the reference preparation, the docetaxel liposomes injection has a much more higher concentration in plasma and sustained-release characteristics, which ameliorated the pharmacokinetic properties of docetaxel.