摘要
目的建立beagle犬血浆中及SD大鼠组织中多西他赛的浓度测定方法,并对新剂型及原有剂型多西他赛药代动力学及组织分布特点进行比较。方法采取双处理、两周期随机交叉的实验设计,观察了在相同剂量(1.0或2.5 mg/kg)下注射用多西他赛和原剂型多西他赛注射液在beagle犬体内的药代动力学差异;观察了两种剂型在大鼠组织中分布的差异;建立了液相色谱-三重串联四级杆质谱联用(QQQ LC-MS)法,测定不同时间的两种剂型多西他赛血浆浓度。结果血浆样品在2～500μg/L范围内呈线性,最低检测限为2μg/L。血浆药物浓度在5、50和500μg/L,日间精密度分别为3.9%、7.0%和5.3%,回收率范围为89.2%～101.1%。血浆样品3日内,萃取样品3个月内稳定性良好。新剂型与原有剂型的药代动力学重要参数差异均有统计学意义(P<0.05),组织学分布可观察到差异。结论建立方法灵敏可靠,满足测定要求。与原剂型相比,在相同剂量下新剂型在血浆中的暴露较低,但是在组织器官中的分布更多,尤其在肺脏中分布更多,持续时间更长。
Objective To establish a liquid chromatography tandem mass spectrometric method for determination of docetaxel in bio-samples and to compare the pharmacokinetic parameters and tissue distribution between novel preparation and original preparation.Methods Two-treatment and two-period random cross-over design were used in this study.Two preparations of deocetaxel were given to beagle dogs at the doses of 1.0 or 2.5 mg/kg.The differences in indicators of pharmacokinetics were observed between treatment groups.And the method of liquid chromatography QQQ mass spectrometric（QQQ LC-MS） was established to detect the blood docetaxel concentration in different periods.Results Docetaxel concentration was linear over the range of 2-500 μg/L and the limit qualification was 2μg/L.The intra-day precision（RSD） ranged from 3.9% to 7.0%.Extraction recovery was above 89.2% for the concentration of 5,50,500 μg/L of samples respectively.The difference of pharmacokinetic parameters and tissue distribution between two preparations were significant.Conclusion The established method was sensitive,fast and simple.The novel preparation was shown lower exposure in plasma while higher exposure in tissue than the original one,especially in lungs.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2011年第4期252-256,共5页
Journal of Toxicology
关键词
多西他赛
高效液相色谱-质谱联用法
药代动力学
组织分布
Docetacel
Liquid chromatography QQQ mass spectrometric（QQQ LC-MS）
Pharmacokinetics
Tissue distribution
