LC-MS/MS同时测定大鼠血浆中的托莫西汀与牛磺酸及其药动学研究  

Simultaneous determination of Atomoxetine and Taurine in the rat plasma by LC-MS/MS and its pharmacokinetics study

作　　者：梁敏[1] 岳山岚 薛金涛[2] 熊冬梅[1] 陈聪[1] 刘振[1] 叶利明[1] 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]新乡医学院,河南新乡453003

出　　处：《华西药学杂志》2016年第3期247-250,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的 采用LC-MS/MS法同时测定大鼠血浆中的托莫西汀与牛磺酸,比较托莫西汀单独给药与托莫西汀联合牛磺酸给药两种方式下托莫西汀的药动学参数。方法 色谱柱为Inertsil ODS-3（100 mm×2.1 mm,5μm）,流动相为含0.2%甲酸的甲醇-20 mmol·L-1乙酸铵的水溶液（80∶20）,流速0.3 m L·min-1;质谱采用电喷雾接口,正离子模式,多反应监测。结果托莫西汀和牛磺酸的线性范围分别为0.935～935 ng·m L-1和0.564~112.8μg·m L-1（r2〉0.99）,最低定量限分别为0.935ng·m L-1、0.564μg·m L-1;方法的日内和日间精密度均〈5.25%;稳定性试验证明牛磺酸和托莫西汀比较稳定。结论 所用方法灵敏度高,选择性好,分析速度快,可用于同时测定血浆中托莫西汀与牛磺酸的含量;在牛磺酸辅助托莫西汀用于治疗注意力缺陷障碍时,托莫西汀的药动学参数与单用托莫西汀时的相比无显著性差异。OBJECTIVE To establish an LC-MS/MS method for simultaneous determination of Atomoxetine（Ato） and Taurine（Tau） in the rat plasma,and to compare the pharmacokinetic differences between single dosed Ato and simultaneously dosed Ato andTau.METHODS The chromatographic separation of analytes was achieved by an Inertsil ODS-3 column（100 mm × 2.1 mm,5 μm）with a mobile phase consisting of 20 mmol·L-1ammonium acetate in water and 0.2% formic acid in methanol（20∶80） at a flow rate of 0.30 m L·min-1.MS was carried out in MRM mode using a positive ESI interface.RESULTS The linear ranges were 0.935-935ng·m L-1for Ato（r2 〉0.99） and 0.564-112.8 μg·m L-1for Tau（r2 〉0.99）.The LOQ were 0.935 ng·m L-1and 0.564 μg·m L-1for Ato and Tau,respectively.The inter-and intra-day precision of the method were less than 5.25%.Stability studies showed that Ato and Tau were stable in the rat plasma for short-and long-term period.CONCLUSION This validated method is selective,sensitive and rapid,and it could be applied to the simultaneous determination of Ato and Tau in the rats plasma.The study shows that the pharmacokinetic of the Ato in rats don＇t have the significant difference between the single administration of Ato and the additional administration of Tau as expulsive treatment for the attention deficit hyperactivity disorder.

关 键 词：托莫西汀 牛磺酸 HPLC-MS/MS 测定 药动学 血药浓度 注意力缺陷障碍 

分 类 号：R917[医药卫生—药物分析学]