YM0402对映体与大鼠血浆蛋白结合率研究

The Rat Plasma Protein Binding of YM0402 Enantiomers

摘要: 目的：明确YM0402对映体与大鼠血浆蛋白结合是否存在立体选择性差异，揭示两对映体与血浆蛋白结合时的相互作用。方法：本研究通过平衡透析法对YM0402对映体与大鼠血浆进行共孵育，并利用手性高效液质联用法进行定量检测。结果：YM0402对映体与大鼠血浆蛋白在考察浓度范围内(0.2~20 μM)结合率均高于90%；在低浓度范围(0.2、1 μM)，A-YM0402的结合率略高于B-YM0402；高浓度下(大于5 μM) YM0402对映体与大鼠血浆蛋白结合趋于饱和。外消旋体中两个异构体的结合率均比单独结合时高。结论：YM0402对映体与大鼠血浆蛋白具有高结合率。两对映体与大鼠血浆蛋白结合可能具有不同位点。

Abstract: OBJECTIVE: To study the stereo selective protein binding of YM0402 enantiomers in rat plasma, and to clarify the interactions between YM0402 enantiomers. METHODS: Equilibrium dialysis method combined with liquid chromatograpy-tandem mass spectrometry was employed to determine the protein binding rate with rats plasma protein. RESULTS: The rat plasma protein binding of YM0402 enantiomers was 90% - 99%. A-YM0402 showed slightly higher binding rate than that of B-YM0402. The bounding rate of both enantiomers in racemate form was higher than that of single enantiomers. CONCLUSION: The binding rate of YM0402 enantiomers with rat plasma protein was higher than 90%. There might be different binding site on rat plasma protein with YM0402 enantiomers.