不同纯度高良姜素的药代动力学比较研究

目的研究不同纯度高良姜素(galangin,GL)在大鼠体内的药代动力学。方法取健康SD大鼠(240～300)g随机分组,每组6只,单次口服给药后尾静脉分时采血、处理。采用反相高效液相色谱法,以外标法测定GL在大鼠血浆中的浓度,应用DAS2.0软件计算主要药代动力学参数。结果在所建立的方法学下,GL在0.05～1.8 mg.L-1的血浆浓度范围内呈良好的线性关系,最低检测限为0.03 mg.L-1(S/N=3),在0.24、0.47、0.94 mg.L-1 3个浓度下的绝对回收率为75.5%～86.9%,相对回收率为85.8%～91.2%,日内和日间RSD均小于5.0%(n=5)。按100 mg.kg-1单次口服给药后,GL在大鼠体内的药代动力学过程均符合二室模型,主要药代动力学参数T12α、T12β、Ka、AUC、Cl/F、V1/F,90%GL分别为19.415 min、33.983 min、0.059 min-1、101.722 mg.min.L-1、0.983 L.min-1.kg-1、5.073 L.kg-1;99%GL分别为24.398 min、31.719 min、0.048 min-1、55.201 mg.min.L-1、1.812 L.min-1.kg-1、6.861 L.kg-1。结论所建立的方法简便、准确、快速,能够满足GL的药代动力学要求。GL纯度为99%时较90%吸收缓慢,消除快。

A comparative study of pharmacokinetics of different purity galangin

Aim To investigate the pharmacokinetics of different purity galangin(GL)in rats in vivo.Methods SD rats were used throughout the experiment and their body weights ranged from 240 to 300 g.All of them were distributed randomly to different test groups(6 rats per group).GL was administered at a single dose via tail vein.The blood was collected from the tail vein plexus at different time points.A reversed-phase high performance liquid chromatography(RP-HPLC) method,in which the external standard method was used,was developed to determine concentrations of GL in rats.The main parameters of pharmacokinetics were calculated by DASS 2.0 software.Results Under the established conditions of HPLC,GL had a validated quantitation ranging from 0.05 mg·L-1 to 1.8 mg·L-1.The lower limit of detection(LLOD) in plasma was 0.03 mg·L-1(S/N=3).At the concentrations of 0.24,0.47,0.94 mg·L-1,absolute recovery were ranged from 75.5% to 86.9%,relative recovery were ranged from 85.8% to 91.2%.The RSD of the precision intra-and inter-day were less than 5.0%(n=5).The concentration-time course of GL was best fitted to a two-compartment open model after a single oral administration dose of 100 mg·kg-1,which the main pharmacokinetic parameters T1 2α,T1 2β,Ka,AUC,Cl/F and V1/F were 19.415 min,33.983 min,0.059 min-1,101.722 mg·min·L-1,0.983 L·min-1·kg-1 and 5.073 L·kg-1 for GL of 90%;24.398 min,31.719 min,0.048 min-1,55.201 mg·min·L-1,1.812 L·min-1·kg-1 and 6.861 L·kg-1 for GL of 99%,respectively.Conclusion The developed method is shown to be simple,accurate and rapid,and can satisfy the requirement of pharmacokinetic study of GL in rat.GL at a high purity is absorbed more slowly and eliminated faster than that at a relatively low purity after a single oral administration dose of 100 mg·kg-1 in rats.