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目的:应用高效液相质谱(HPLC-MS)法研究血塞通对氯沙坦钾大鼠体内药动学的影响。方法:大鼠分别口服氯沙坦钾和氯沙坦钾加血塞通后,采用HPLC-MS法检测氯沙坦钾及代谢产物EXP3174的血药浓度,计算相关药动学参数,并进行统计学分析。结果:氯沙坦钾及代谢物EXP3174在2.0~2 000 ng·ml~(-1)的浓度范围内线性关系良好(r=0.996 4和r=0.999 5);平均回收率为85.19%~109.79%。样品测定结果显示:联合用药后,氯沙坦钾的t_(1/2)和V_z/F显著减小(P<0.05),T_(max)显著增加(P<0.05);代谢物EXP3174的t_(1/2)显著减小(P<0.05),T_(max)显著增加(P<0.05)。结论:所建立的HPLC-MS法灵敏度高、选择性好,可用于体内氯沙坦钾及EXP3174血药浓度的测定。血塞通与氯沙坦钾联用后,能够影响氯沙坦钾在体内的吸收与代谢。
Objective: To study the effect of Xuesaitong on the pharmacokinetics of losartan potassium in rats by high performance liquid chromatography-mass spectrometry (HPLC-MS). Methods: After oral administration of losartan potassium and losartan potassium plus Xuesaitong, the plasma concentrations of losartan potassium and its metabolite EXP3174 were determined by HPLC-MS, and the related pharmacokinetic parameters were calculated and statistically analyzed Analysis. RESULTS: Losartan potassium and its metabolite EXP3174 had a good linear relationship (r = 0.996 4 and r = 0.999 5) in the concentration range of 2.0-2000 ng · ml -1 with an average recovery of 85.19% -109.79 %. The results of sample analysis showed that t_ (1/2) and V_z / F of losartan potassium decreased significantly (P <0.05) and T max increased significantly (P <0.05) (1/2) significantly decreased (P <0.05) and T max increased significantly (P <0.05). Conclusion: The established HPLC-MS method has high sensitivity and good selectivity and can be used for the determination of losartan potassium and EXP3174 blood concentration in vivo. Xuesaitong combined with losartan potassium, can affect the absorption and metabolism of losartan potassium in the body.