摘要
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.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2007年第5期367-370,共4页
Chinese Journal of New Drugs and Clinical Remedies
关键词
多西他赛
脂质体
药动学
色谱法
高压液相
光谱法
质量
电喷雾电离
docetaxel
liposomes
pharmacokinetics
chromatography, high pressure liquid
spectrometry, mass, electrospray ionization