Tudy on drug displacement interactions by capillary electrophoresis-frontal analysis

Abstract

The interaction between 18-methyl norethindrone and ketoprofen, including the displacement of ketoprofen from human serum albumin binding sites, was investigated by the 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^-1 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 can displace ketoprofen from its secondary binding site.

Keywords

capillary electrophoresis-frontal analysis, human serum albumin, displacement interaction