8-乙酰哈巴苷大鼠体内药代动力学

Pharmacokinetic of 8-acetylharpagide in Rats

目的:建立血浆中8-乙酰哈巴苷的HPLC测定方法,研究大鼠不同给药途径给予8-乙酰哈巴苷后的药代动力学特征。方法:大鼠分别注射和灌胃8-乙酰哈巴苷,于不同时间点取血;采用HPLC,流动相乙腈-异丙醇-水(1.8∶10.2∶88),检测波长207 nm,流速1.0 mL.min-1,绘制药-时曲线,建立药代动力学模型,计算药代动力学参数。结果:8-乙酰哈巴苷在血浆中的回归方程为Y=613 753.13X-86 995.55(r=0.999 2),在0.015 3～22.995μg线性关系良好。高、中、低3个剂量组日内精密度RSD分别为0.59%,0.38%,0.55%;日间精密度RSD分别为3.9%,2.1%,1.5%。回收率分别为94.89%,95.85%,95.25%。灌胃途径在体内基本检测不出;注射途径3个剂量组主要药代动力学参数t1/2分别为(21.15±3.36),(24.26±5.50),(16.58±5.65)min;tmax分别为(4.98±0),(4.98±0),(4.98±0)min;Cmax分别为(2.25±1.41),(0.09±0.03),(0.02±0.007)g.L-1。结论:该法灵敏度高,专属性强,准确可靠,操作快速简便,可用于8-乙酰哈巴苷在大鼠体内的药代动力学研究,注射给予8-乙酰哈巴苷在大鼠体内吸收快且不完全,消除相对较慢,但具有良好的药代动力学特征,房室模型拟合分析为一房室模型。

Objective： To establish a plasma 8-acetylharpagide in HPLC determination of Khabarovsk to study different routes of administration in rats given 8-acetylharpagide Haba pharmacokinetics after.Method： Rats were injected and orally 8-acetylharpagide,blood was collected at different time points;detected in plasma by HPLC 8-acetylharpagide,acetonitrile-isopropyl alcohol-water（1.8∶10.2∶88）,detection wavelength 207 nm,flow rate 1.0 mL · min-1,draw the curve,the establishment of pharmacokinetic models,calculation of pharmacokinetic parameters.Result：Regression equation of 8-acetylharpagide in plasma was Y=613 753.13X-86 995.55（r=0.999 2）.In the range of 0.015 3-22.995 μg with good linear relationship.The intra-day and inter-day precision of three dosage were 0.59%,0.38%,0.55%;3.9%,2.1%,1.5% respectively.The extraction recoveries were 94.89%,95.85%,95.25%.The intragastric approach basically can not be detected in thebody;The main pharmacokinetic parameters of injection means by three dosage group were as follows：t1/2（21.15±3.36）,（24.26±5.50）,（16.58±5.65） min;tmax（4.98±0）,（4.98±0）,（4.98±0） min;Cmax（2.25±1.41）,（0.09±0.03）,（0.02±0.007） g·L-1.Conclusion： This method was proved to be sensitive,selective and simple.It can be successfully applied to the pharmacokinetic study of 8-acetylharpagide.The injection given to 8-acetylharpagide in rats in vivoabsorption of Khabarovsk fast and does not completely eliminate relatively slow,but with good pharmacokinetic characteristics,compartment model fitting analysis for the compartment model.