【摘要】 目的:建立测定人血浆中噻托溴铵浓度的方法,考察健康志愿者口腔吸入噻托溴铵粉雾剂1粒后的主要药动学参数。方法:以C18固相萃取小柱提取浓缩血浆中的活性成分tiotropium(含tiotropium 18μg)后进行液-质联用(LC-MS)法分析,流动相为40 mmol/L乙酸铵缓冲液-甲醇(56∶44);检测离子分别为m/z 392.0(tiotropium[M]+)、m/z 192.3(内标,[M-Cl]+),裂解电压为200V。结果:tiotropium血药浓度在1.507~30.15 pg/ml范围内线性关系良好(r=0.999 6),最低定量限为1.507 pg/ml;日内、日间RSD均≤7%,相对回收率为100.6%~108.6%,提取回收率为89.2%~96.4%。男女受试者的药动学参数分别为:t1/2(103.7±14.6)、(110.9±14.6)h,tmax(8.3±5.2)、(8.3±5.2)h,cmax(16.65±8.22)、(16.26±3.10)pg/ml,AUC0-24 h(60.9±15.1)、(62.4±7.8)pg·h/ml。结论:本试验建立的分析方法灵敏、准确、简便。更多还原

【Abstract】 OBJECTIVE:To develop a method for the determination of tiotropium in human plasma and to investigate main pharmacokinetic parameters of tiotropium in healthy volunteers after oral inhalation of Tiotropium bromide inhalation powder.METHODS:C18 solid phase extraction column was used to extract tiotropium(18 μg)and analyzed by LC-MS.The mobile phase consisted of 40 mmol/L ammonium acetate buffer solution-methanol(56∶44).The selected ion monitoring(SIM)mode used target ions at m/z 392.0 for tiotropium([M]+)and m/z 192.23 for benzyltriethyl ammoniachloride(IS,[M-Cl]+).The fragmentary voltage was 200 V.RESULTS:The linear range of tiotropium was 1.507-30.15 pg/ml(r=0.999 6).The lowest limit of quantification was 1.507 pg/ml.RSD of inter-day and intra-day were all lower than 7%;relative recoveries in male and female were 100.6%-108.6% and extraction recoveries were 89.2%-96.4%.The main pharmacokinetic parameters of tiotropium were as follows:t1/2(103.7± 14.6)h and(110.9±14.6)h;tmax(8.3±5.2)h and(8.3±5.2)h;cmax(16.65±8.22)pg/ml and(16.26±3.10)pg/ml;AUC0-24 h(60.9±15.1)pg·h/ml and(62.4±7.8)pg·h/ml.CONCLUSIONS:The method is proved to be sensitive,accurate and convenient.更多还原