目的建立快速、灵敏的卢帕他定人体内血药浓度的液相色谱-质谱测定法,并对10名健康志愿者口服富马酸卢帕他定片后在人体内的药动学过程进行研究。方法10名健康志愿者单剂量口服给药10mg后,分别于给药前和给药后0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,16及24h采集血样。用高效液相色谱-质谱法测定血浆中卢帕他定的浓度,并采用PKS药动学程序对试验数据进行处理,求算有关药动学参数。结果单剂量口服给药富马酸卢帕他定片10mg后,其药-时曲线拟合符合二室模型,t_1/2,t_max,ρ_max,AUC_0-24,AUC_0-∞分别为(5.3±1.7)h,(0.8±0.1)h,(2.38±0.61)μg·L^-1,(6.8±1.2)μg·h·L^-1,(7.3±1.3)μg·h·L^-1。结论试验建立的卢帕他定人体内血药浓度测定方法灵敏、可靠、简便;富马酸卢帕他定片单剂量给药后在中国健康人体内的药动学行为与国外文献报道基本一致。

OBJECTIVE To develop a rapid and sensitive HPLC-MS method for the analysis of rupatadine in human plasma,and study the pharmacokinetic characteristics of rupatadine fumarate tablets after a single oral dose of 10 mg in healthy volunteers.METHODS A single oral dose of 10 mg rupatadine fumarate tablets was given to 10 healthy volunteers.Blood samples were collected before dosing and at 0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,16,24 h after a single oral dose of 10 mg.A HPLC-MS method was used to assay the concentration of rupatadine in plasma.The pharmacokinetic parameters were evaluated with PKS program.RESULTS The concentrations of rupatadine in plasma were discribed with a two-compartment model.The main pharmacokinetic parameters of rupatadine by oral administration were as follows:t_1/2(5.3±1.7)h,t_max(0.8±0.1)h,ρ_max(2.38±0.61)μg·L^-1,AUC_0-24(6.8±1.2)μg·h·L^-1,AUC_0-∞(7.3±1.3) μg ·h·L^-1.CONCLUSION The analytical method appeared to be accurate,sensitive and convenient.The pharmacokinetic profile of rupatadine fumarate tablet was similar to the published reports.