LC-MS/MS法测定大鼠体内多西他赛血药浓度及其药动学研究

Study on Plasma Concentration and Pharmacokinetics of Docetaxel in Rats by LC-MS/MS

目的:建立测定大鼠血浆样品中多西他赛浓度的方法,并进行药动学研究。方法:以紫杉醇为内标,取8只大鼠尾静脉单剂量注射多西他赛5mg·kg-1,分别于给药前和给药后2、15、30、90、240、480、720、1440min眼眶后静脉丛采血,采用液相色谱-串联质谱法测定其血药浓度,并计算药动学参数。结果:多西他赛在大鼠体内的药-时曲线符合三室模型,主要药动学参数t12z为(236.44±53.47)min,c0为(3.84±0.97)mg·L-1,AUC(0～t)为(66.66±11.39)mg·min·L-1。结论:本方法专属性好、准确度好、灵敏度好,可为今后临床患者血药浓度监测和药动学研究提供方法学依据。

OBJECTIVE： To establish the method for the determination of plasma concentration of docetaxel in rat and to study its pharmacokinetics. METHODS： 8 rats were given single dose of docetaxel 5 mg·kg-1 through tail vein with paclitaxel as internal standard. Blood sample was collected from post-eyelid vein before medication and 2 min, 15 min, 30 min, 90 min, 240 min, 480 min, 720 min, 1 440 min after medication. The plasma concentration of docetaxel was determined by LC-MS/MS and pharmacokinetic parameters were calculated. RESULTS： Mean plasma concentration-time curve of docetaxel in rats was in line with three-compartment model. Main pharmacokinetic parameters were as follows： t1/2z：（236.44±53.47） min,c0：（3.84±0.97） mg·L-1,AUC（0～t）：（66.66±11.39） mg·min·L-1. CONCLUSION： The method is specifical, accurate and sensitive. It provides methodological evidence for plasma concentration monitoring and pharmacokinetic study of docetaxel.