药物间置换相互作用的毛细管电泳迎头分析法研究

Study on Drug Displacement Interactions by Capillary Electrophoresis-Frontal Analysis

将 18 甲基炔诺酮加到人血清白蛋白 酮洛芬平衡溶液中,室温孵育达平衡后应用毛细管电泳 迎头分析法研究了 18 甲基炔诺酮和酮洛芬在人血清白蛋白分子上的置换相互作用。一大体积样品虹吸进样至未涂层毛细管(65cm×50μmi d ,有效长度 35cm),进样时间 80s,毛细管两端高度差 11cm,工作电压 10kV,运行缓冲液为67mmol/L磷酸盐缓冲液(pH7 4),游离酮洛芬浓度由前沿峰的高度直接测定。当酮洛芬样品溶液中酮洛芬的总浓度分别为 100μmol/L和 200μmol/L时,随着 18 甲基炔诺酮加入量的增加 (18 甲基炔诺酮的浓度由 0增至 200μmol/L),游离酮洛芬的浓度分别从 22 4增至 26 4μmol/L和从 82 1增至 106 2μmol/L。由上面的结果可推论:高浓度的 18 甲基炔诺酮可将酮洛芬从它的第二类结合位点上置换出来。

The interaction between 18-methyl norethindrone and ketoprofen including the displacement of ketoprofen from human serum albumin binding sites was investigated by capillary electrophoresis-frontal analysis method (CE-FA) at room temperature. A very large sample plug was introduced hydrostatically into the capillary (65 cm×50 μm i.d., effective length of 35 cm) over 80 s at a height difference of 11 cm. The working conditions for CE-FA separation are as follows: operating voltage, 10 kV; running buffer, 67 (mmol/L) phosphate, pH 7.4. The unbound ketoprofen concentration was directly measured from the height of the frontal peak. When the concentration of 18-methyl norethindrone was increased from 0 to 200 (μmol/L), the unbound ketoprofen concentration was found to increase from 22.4 to 26.4 (μmol/L) at 100(μmol/L) total ketoprofen concentration and from 82.1 to 106.2 (μmol/L) at 200 (μmol/L) total ketoprofen concentration. From these data, it may be deduced that the administration of high concentration of 18-methyl norethindrone could displace ketoprofen from its (secondary) binding site.