【摘要】 目的：建立一种高灵敏液相色谱串联质谱法（LC-MS/MS）测定健康志愿者经口吸入噻托溴铵粉吸入剂1粒（18μg）后血浆中噻托溴铵的含量,并评价其药代动力学特征。方法：14名健康志愿者空腹经口吸入噻托溴铵粉1粒（18μg）后采集静脉血，血浆样品在冰浴条件下，加入内标噻托溴铵-d6，再经过含1%甲酸的乙腈溶液蛋白沉淀后，采用ACE Excel 3 AQ(100mm×2.1mm,3μm,ACE)色谱柱分离，在正离子模式下以多重反应监测方式进行检测。结果：噻托溴铵在（0.1～16）pg·mL-1浓度范围内线性关系良好，健康志愿者吸入噻托溴铵的Cmax为（5.21±3.22）pg·mL-1、AUC0-t和AUC0-∞分别为（30.0±11.8）h·pg·mL-1和（48.8±15.5）h·pg·mL-1, tmax为（0.064±0.035）h,t1/2为（76.0±23.7）h。结论：本方法可用于噻托溴铵吸入粉剂的人体药代动力学研究。更多还原

【Abstract】 Objective: To develop a sensitive LC-MS/MS method for the determination and pharmacokinetic evaluation of tiotropium in human plasma after oral inhalation of tiotropium bromide inhalation powders(18 μg).Methods: Blood samples of 14 healthy volunteers were collected after oral inhalation of tiotropium bromide inhalation powders(18 μg). Plasma samples were pre-treated by protein precipitation with 1% formic acid acetonitrile solution in ice water bath, tiotropium-d6 was used as the internal standard. Chromatographic separation was performed using an ACE Excel 3 AQ(100 mm × 2.1 mm, 3 μm) column. The mass spectrometric(MS) detection was operated in the positive ion mode using multiple reaction monitoring(MRM). Results:The LC-MS/MS method had linear calibrations over 0.1-16 pg·mL-1ranges. For oral inhalation of tiotropium bromide inhalation powders(18 μg), Cmaxwas(5.21 ± 3.22) pg·mL-1, AUC0-tand AUC0-∞were(30.0 ± 11.8)h·pg·m L-1and(48.8 ± 15.5)h·pg·mL-1, tmaxwas(0.064 ± 0.035)h and t1/2was(76.0 ± 23.7)h. Conclusions: The established LC-MS/MS method can be applied to the pharmacokinetic study of tiotropium bromide inhalation powders in human plasma.更多还原