非索非那定体内探针药物法考察脑心通胶囊对大鼠P-gp活性的影响

Modulation of rat P-gp by multiple doses of Naoxintong capsule using fexofenadine as a phenotyping probe

关键词:  液相色谱-质谱联用法  非索非那定  脑心通  P-糖蛋白

Key words:  LC-MS/MS  fexofenadine  Naoxintong  P-gp

摘要:

[目的]建立检测大鼠血浆中非索非那定的液相质谱联用（LC-MS/MS）方法，考察脑心通胶囊对大鼠P糖蛋白（P-gp）的影响。[方法]采用Waters XBridge^TM C₁₈（2.1 mm×100 mm，3.5 μm）色谱柱，以乙腈-0.1%甲酸水为流动相进行梯度洗脱，电喷雾离子源，多反应正离子模式监测，用于定量分析的离子反应分别为m/z 502.3→466.3（非索非那定），m/z 256.1→166.9（内标，苯海拉明）。[结果]非索非那定在1~250 ng/mL范围内线性关系良好，日内、日间精密度（RSD）均小于8.7%，方法回收率均大于83.0%。[结论]该方法灵敏、可靠，可用于快速检测大鼠血浆中的非索非那定。大鼠经连续灌胃给药脑心通胶囊后可对大鼠体内P-gp的活性产生抑制作用。

Abstract:

[Objective] A liquid chromatography tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination of fexofenadine in rats plasma, and the effects of Naoxintong on P-gp in rats were studied.[Methods] The samples were separated on a Waters XBridge^TM C₁₈ column (2.1 mm×100 mm, 3.5 μm) with a gradient mobile phase system of 0.1% (V/V) formic acid and acetonitrile. Fexofenadine and diphenhydramine (Internal Standard) were detected by electrospray ionization (ESI) with multiple reaction monitoring. The transitions at m/z 502.3 → 466.3 (fexofenadine), and m/z 256.1 → 166.9 (IS), respectively.[Results] A good linear response was observed over the concentration ranges of 1-250 ng/mL. Both intra and inter-day precision (RSD) were within 8.7%, and the extraction recovery were more than 83.0%.[Conclusion] The results suggested that the method proved to be highly reproducible and sensitive that was successfully applied in the pharmacokinetic study of fexofenadine, and the inhibitory effect of Naoxintong capsule on the activity of P-gp in rats after continuous administration of Naoxintong were observed.