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目的:为临床研究阿齐沙坦人体药动学建立一种高效、专一的液相色谱-串联质谱(LC-MS/MS)方法,并将其应用于阿齐沙坦在中国健康人群药动学研究。方法:含阿齐沙坦血浆样本与内标混合后经乙腈处理,以含5 mmol·L~(-1)甲酸铵溶液-乙腈为流动相,SB-Aq色谱柱(3.0 mm×100 mm,3.5μm)为分析柱,采用API 4000型液质联用系统,流速0.6 m L·min~(-1),室温下测定;采用负离子模式,MRM扫描,阿齐沙坦m/z 455.2→411.2和内标奥美拉唑m/z 344.1→193.9。9例健康受试者口服40 mg阿齐沙坦片,于不同时间点分别采集静脉血进行药代动力学分析。结果:阿齐沙坦和内标的保留时间分别为4.17和4.77 min,标准曲线在0.01~10.0 mg·mL~(-1)范围内线性良好(r=0.998 6±0.000 9),最低定量限10 ng·mL~(-1),日内、日间批间差异均小于12%,准确度在89.2%~110.2%,回收率在83.2%~96.2%之间,所有的稳定性考察项目均符合要求。药动学结果显示,健康受试者口服阿齐沙坦片40 mg后,阿齐沙坦在人体内平均达峰时间t_(max)=2.22 h,平均半衰期t_(1/2_=10.15 h。结论:本测定方法适用于阿齐沙坦的药动学研究和血药浓度监测。
OBJECTIVE: To establish an efficient and specific liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the clinical pharmacokinetics of azilsartan in human beings and to apply Azilsartan in Chinese healthy people Kinematics research. Methods: The plasma samples of Azithromycin were mixed with internal standard and then treated with acetonitrile. The mobile phase consisted of 5 mmol·L -1 ammonium formate - acetonitrile, and the mobile phase was SB-Aq (3.0 mm × 100 mm, 3.5μm) was used as the analytical column. The flow rate was 0.6 m L · min ~ (-1) at room temperature using the API 4000 LC / MS system. Negative ion mode, MRM scanning, Azizartan m / z 455.2 → 411.2 And internal standard omeprazole m / z 344.1 → 193.9.9 healthy subjects oral administration of 40 mg of Azilsartan tablets at different time points were collected venous blood for pharmacokinetic analysis. Results: The retention times of Azilsartan and internal standard were 4.17 and 4.77 min, respectively. The calibration curve was linear over the range of 0.01-10.0 mg · mL -1 (r = 0.998 6 ± 0.000 9). The lowest limit of quantification was 10 ng · mL ~ (-1). The difference between days and days was less than 12%, the accuracy was between 89.2% and 110.2%, and the recoveries were between 83.2% and 96.2%. All the stability study items met the requirements . Pharmacokinetic results showed that the average peak time of azilsartan in human body after oral administration of 40 mg of azilsartan was t (max) = 2.22 h, with an average half-life of t 1/2 (10.15 h). Conclusion: This method is suitable for the determination of azilsartan pharmacokinetics and plasma concentration monitoring.