目的建立快速、灵敏的佐米曲普坦人体内血药浓度的液相色谱-质谱测定法,并对鼻腔给药佐米曲普坦鼻喷雾剂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鼻腔给药5mg后,分别于给药前和给药后0.25,0.5,0.75,1,1.5,2,2.5,3,4,5,6,8,10,12及14h采集血样。用高效液相色谱-质谱法测定血浆中佐米曲普坦的浓度,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。结果单剂量鼻腔给药佐米曲普坦鼻喷雾剂5mg后,其药-时曲线拟合符合一室模型,ρ_max,t_max,t_1/2,AUC_0-14,AUC_0-∞分别为(10.20±1.40)μg·L^-1,(2.80±0.26)h,(3.58±0.87)h,(37.85±9.19)μg·h·L^-1,(39.94±8.85)μg·h·L^-1。结论试验建立的佐米曲普坦人体内血药浓度测定方法灵敏、简便、可靠;佐米曲普坦单剂量给药后在中国健康人体内耐受良好,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 zolmitriptan in human plasma,and study the pharmacokinetic characteristics of zolmitriptan nasal spray after a single spray dose of 5 mg in healthy volunteers. METHODS A single spray dose of 5 mg Zolmitriptan was given to 10 healthy volunteers. Blood samples were taken for detecting plasma concentration before dosing and at 0.25,0.5,0.75,1,1.5,2,2.5,3,4,5,6,8,10,12,14 h after a single spray dose of 5 mg. A HPLC-MS method was used to assay the concentration of zolmitriptan in plasma. The pharmacokinetic parameters were evaluated with PKS program. RESULTS The concentrations of zolmitriptan in plasma were fitted with an one-compartment model. The main pharmacokinetic parameters of zolmitriptan by spray adminstration were as follows:ρ_max was(10.20±1.40)μg·L^-1,t_max was(2.80±0.26)h, t_1/2 was(3.58±0.87)h,AUC_0-14 was(37.85±9.19)μg·h·L^-1,AUC_0-∞ was(39.94±8.85)μg·h·L^-1. CONCLUSION The analytical method appears to be accurate, sensitive and convenient. Zolmitriptan shows good tolerance in healthy Chinese volunteers after a single spray dose. The pharmacokinetic characteristics of zolmitriptan nasal spray are similar to the foreign reports.