Evalution of capillary electrophoresis-frontal analysis for the study of low molecular weight drug-human serum albumin interactions.
Capillary electrophoresis frontal analysis was applied to 12 low molecular weight compounds including 8 drug substances displaying a range of different properties with respect to binding affinity, binding location, structure, lipophilicity, charge at physiological pH, and electrophoretic mobility. It was found that capillary electrophoresis frontal analysis can be used as a general method to study and quantify drug-human serum albumin interactions. The binding parameters obtained were consistent with literature values. Dextran was in some cases added to the run buffer to improve separation of the drug and human serum albumin plateau peaks. Results indicate that mobility differences between free and complexed human serum albumin give rise to only minor errors. Capillary electrophoresis frontal analysis was also found applicable to the study of human serum albumin drug displacement reactions. Low sensitivity of the UV-detection system was found to be the major limitation of capillary electrophoresis frontal analysis. The method is simple, and minimal effort has to be put into method development, which makes it well suited for screening in early drug development.
Department of Analytical and Pharmaceutical Chemistry, Royal Danish School of Pharmacy.
Jesper
J
Østergaard
Christian
C
Schou
Claus
C
Larsen
Niels H H
NH
Heegaard
D001667:Binding, Competitive; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010599:Pharmacokinetics; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D012709:Serum Albumin