| 引用本文: | 徐玲玲,王芳,王本伟,刘小雨,逯海燕,刘爱明,贾庆文,戚敏.LC-MS/MS测定阿齐沙坦及其盐在大鼠血浆中的药动学研究[J].中国现代应用药学,2019,36(20):2561-2564. |
| XU Lingling,WANG Fang,WANG Benwei,LIU Xiaoyu,LU Haiyan,LIU Aiming,JIA Qingwen,QI Min.Study on Pharmacokinetics of Azilsartan and Its Salt in Rat Plasma by LC-MS/MS[J].Chin J Mod Appl Pharm(中国现代应用药学),2019,36(20):2561-2564. |
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| 摘要: |
| 目的 建立液相色谱-串联质谱法测定大鼠血浆中阿齐沙坦及其盐的浓度并研究其药动学。方法 大鼠血浆样本以乙腈沉淀蛋白后，采用Eclipse Plus C18色谱柱（50 mm×3.0 mm，1.8 μm）；流动相（乙腈：水=60：40），流速为0.35 mL·min-1，柱温为40℃；采用Agilent 6430三重四极杆串联质谱仪，离子化方式：电喷雾-正离子（API-ES）；监测方式：MRM；阿齐沙坦监测离子对457.3/233.1，缬沙坦监测离子对436.2/291.4，用作内标。SD大鼠灌胃给予阿齐沙坦1.0 mg·kg-1及阿齐沙坦盐1.2 mg·kg-1。结果 阿齐沙坦在5~30 000 ng·mL-1内线性关系良好；回收率为85%~115%，精密度RSD在±15%内。阿齐沙坦盐大鼠体内主要动力学参数如下：AUC（0-24 h）为（12.9±3.2）μg·mL-1·h-1，AUC（0-∞）为（14.2±4.1）μg·mL-1·h-1，Cmax为（3.8±0.3）μg·mL-1，T1/2为（13.4±0.5）h。阿齐沙坦的主要动力学参数如下：AUC（0-24 h）为（8.1±2.6）μg·mL-1·h-1，AUC（0-∞）为（9.7±3.1）μg·mL-1·h-1，Cmax为（2.3±0.5）μg·mL-1，T1/2为（10.5±0.5）h。结论 本法经方法学验证，适用于大鼠血浆中阿齐沙坦及其盐的浓度测定，可用于阿齐沙坦及其盐大鼠体内药动学研究。 |
| 关键词: 阿齐沙坦 盐 大鼠血浆 液相色谱-串联质谱法 药动学 |
| DOI：10.13748/j.cnki.issn1007-7693.2019.20.015 |
| 分类号:R917.101 |
| 基金项目: |
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| Study on Pharmacokinetics of Azilsartan and Its Salt in Rat Plasma by LC-MS/MS |
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XU Lingling, WANG Fang, WANG Benwei, LIU Xiaoyu, LU Haiyan, LIU Aiming, JIA Qingwen, QI Min
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Shandong Academy of Pharmaceutical Sciences, Jinan 250101, China
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| Abstract: |
| OBJECTIVE To establish an LC-MS/MS method to determine azilsartan and its salt in rat plasma and investigate their pharmacokinetics. METHODS After protein precipitation with acetonitrile, the analytes and internal standard were separated on Eclipse Plus C18 column(50 mm×3.0 mm, 1.8 μm) with acetonitrile-water (60:40) as mobile phase eluted at a flow rate of 0.35 mL·min-1. Detection was carried out by electrospray positive ionization mass spectrometry in the multiple reaction monitoring(MRM) mode. The MRM transitions of m/z 457.3/233.1 and m/z 436.2/291.4 were used to quantify azilsartan and valsartan, respectively. SD rats were given azilsartan of 1.0 mg·kg-1 while the salt of 1.2 mg·kg-1. RESULTS The calibration curve of azilsartan was linear over the concentration range of 5-30 000 ng·mL-1. The RSDs of accuracy were <15%. The main pharmacokinetics parameters of the salt in rats were estimated as follows:AUC(0-24 h)was (12.9±3.2)μg·mL-1·h-1, AUC(0-∞) was (14.2±4.1)μg·mL-1·h-1, Cmax was (3.8±0.3)μg·mL-1, T1/2 was (13.4±0.5)h. The main pharmacokinetics parameters of azilsartan were estimated as follows:AUC(0-24 h) was (8.1±2.6)μg·mL-1·h-1, AUC(0-∞) was (9.7±3.1)μg·mL-1·h-1, Cmax was (2.3±0.5)μg·mL-1, T1/2 was (10.5±0.5)h. CONCLUSION The established method can be applied on the determination of azilsartan and its salt in plasma of rats and is suitable for the pharmacokinetics study. |
| Key words: azilsartan salt rat plasma LC-MS/MS pharmacokinetics |
