索拉非尼在人和大鼠血浆中血浆蛋白结合率的测定

Plasma protein binding characteristics of sorafinib in rat plasma and human plasma by equilibrium dialysis method

目的测定索拉非尼在大鼠和人血浆中的血浆蛋白结合率。方法用平衡透析法研究索拉非尼与大鼠血浆和人血浆的蛋白结合率,用高效液相色谱法测定样品中索拉非尼的含量。结果索拉非尼在4. 90,9. 80和19. 60 mg·L-1浓度水平与大鼠的蛋白结合率分别为(99. 36±0. 01)%,(99. 44±0. 06)%和(99. 31±0. 07)%,与人血浆的蛋白结合率分别为(99. 62±0. 01)%,(99. 55±0. 03)%和(99. 53±0. 20)%。索拉非尼在实验浓度范围内与大鼠和健康人血浆均属于高强度结合,索拉非尼与大鼠的血浆蛋白结合率略低于人血浆,2种血浆中索拉非尼血浆蛋白结合率差异无统计学意义(P> 0. 05)。结论建立的索拉非尼蛋白结合率测定方法简便、稳定、可靠,索拉非尼的血浆蛋白结合率不具有明显的浓度依赖性和种属差异。

Objective To study the plasma protein binding rate of sorafinib in rat plasma and human plasma.Methods Equilibrium dialysis method was employed to determine the plasma protein binding rate of sorafinib.The plasma concentrations of sorafinib were measured by HPLC.Results The plasma protein binding rate of sorafinib in rat plasma at the concentration of 4.90,9.80 and 19.60 mg·L-1 were(99.36±0.01)%,(99.44±0.06)%and(99.31±0.07)%,while in human plasma were(99.62±0.01)%,(99.55±0.03)%and(99.53±0.20)%.Plasma protein binding characteristics of sorafinib showed high intensity of binding in rat plasma and human plasma,while the protein binding rates of sorafinib in human plasma was a little higher than in rat plasma.There was no significant difference between plasma protein binding characteristics of sorafinib binding in rat plasma and human plasma(P>0.05).Conclusion This method for determining plasma protein binding rates of sorafinib was simple,stable and reliable.The plasma protein binding rate of sorafinib has no significance concentration dependent and species differences.