Binding analysis of nilvadipine to plasma lipoproteins by capillary electrophoresis-frontal analysis

Capillary electrophoresis coupled with frontal analysis (HPCE/FA) was appli ed to the ultramicro analysis of enantioselective binding of nilvadipine (N V), a calcium channel blocker, to plasma lipoproteins. The drug-lipoprotein mixed solution was hydrodynamically introduced into a non-coated fused sil ica capillary for capillary electrophoresis. Since NV has no electric charg e in the run buffer (pH 7.4), the unbound NV moved towards the cathodic end by electroosmotic flow, which was faster than the electrophoretic migratio ns of negatively charged lipoproteins and the bound NV. Once unbound NV mig rated apart from lipoprotein, and bound NV was quickly released from the pr otein to maintain the binding equilibrium. Thus, NV migrated as a zone with a plateau region. The concentration of NV in this plateau region appearing on the electrophorogram was the same as the unbound NV concentration in th e initial sample solution. It was found that the binding of NV to high-dens ity lipoprotein (HDL), low-density lipoprotein (LDL) and oxidized LDL was n on-specific and not enantioselective. Partition-like binding to the lipid p art of these lipoproteins seemed to occur dominantly. The total binding aff inities of NV to LDL were about seven times stronger than those to HDL, and the oxidation of LDL enhanced the binding affinity significantly. (C) 1999 Elsevier Science B.V. All rights reserved.