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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 determine the determination of tomoxetine and taurine in rat plasma by LC-MS / MS. To compare the effect of tomoxetine alone and in combination with tomoxetine on taurine administration in two modes: Ting pharmacokinetic parameters. Methods The chromatographic column was Inertsil ODS-3 (100 mm × 2.1 mm, 5 μm). The mobile phase consisted of methanol-20 mmol·L-1 ammonium acetate solution (80:20) containing 0.2% formic acid and the flow rate was 0.3 m L · min -1; mass spectrometry using electrospray interface, positive ion mode, multi-reaction monitoring. Results The linear ranges of tomoxetine and taurine ranged from 0.935 to 935 ng · m L-1 and from 0.564 to 112.8 μg · m L-1 (r2> 0.99), with the minimum limits of quantification of 0.935 ng · m L-1 , 0.564μg · m L-1. The intra-and inter-day precision of the method was <5.25%. The stability test showed that taurine and tomoxetine were stable. Conclusion The method used is sensitive, selective and fast in analysis. It can be used for the simultaneous determination of tomoxetine and taurine in plasma. When tauroxamate adjuvant tomoxetine is used to treat attention deficit disorder, There was no significant difference in the pharmacokinetic parameters of moxetine compared with that of tomoxetine alone.