Binding analysis of nilvadipine to plasma lipoproteins by capillary electrophoresis-frontal analysis.
Capillary electrophoresis coupled with frontal analysis (HPCE/FA) was applied to the ultramicro analysis of enantioselective binding of nilvadipine (NV), a calcium channel blocker, to plasma lipoproteins. The drug lipoprotein mixed solution was hydrodynamically introduced into a non-coated fused silica capillary for capillary electrophoresis. Since NV has no electric charge in the run buffer (pH 7.4), the unbound NV moved towards the cathodic end by electroosmotic flow, which was faster than the electrophoretic migrations of negatively charged lipoproteins and the bound NV. Once unbound NV migrated apart from lipoprotein, and bound NV was quickly released from the protein 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 the initial sample solution. It was found that the binding of NV to high-density lipoprotein (HDL), low-density lipoprotein (LDL) and oxidized LDL was non-specific and not enantioselective. Partition-like binding to the lipid part of these lipoproteins seemed to occur dominantly. The total binding affinities of NV to LDL were about seven times stronger than those to HDL, and the oxidation of LDL enhanced the binding affinity significantly.
Mohamed
N A
NA
Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Kuroda
Y
Y
Shibukawa
A
A
Nakagawa
T
T
El Gizawy
S
S
Askal
H F
HF
El Kommos
M E
ME
D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000378:metabolism*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D011485:Protein Binding; D013056:Spectrophotometry, Ultraviolet
D002121:Calcium Channel Blockers; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C035100:nilvadipine; D009543:Nifedipine