High-performance frontal analysis for drug-protein binding study

High-performance frontal analysis (HPFA) is a novel analytical method which enables simultaneous determination of total and unbound drug concentration s under drug-plasma protein binding condition. HPFA can be achieved using s eparation systems such as HPLC and CE. This paper deals with the principle and feature of HPFA method and its application to the stereoselective prote in binding study. HPFA allows a simple analysis following direct sample inj ection, and does not suffer from undesirable drug adsorption on membrane no r leakage of bound drug through the membrane which are often encountered in conventional ultrafiltration and dialysis methods. HPFA can be easily inco rporated into on-line HPLC system. By coupling HPFA with a chiral HPLC colu mn, the unbound concentration of a racemic drug can be determined enantiose lectively. The detection limit can be improved by coupling of HPFA with a p reconcentration column. High-performance capillary electrophoresis/frontal analysis (HPCE/FA) enables to determine unbound concentrations enantioselec tively with ultramicro injection volume, and is hence useful especially for the binding study of proteins which are scarce and difficult to obtain. (C ) 1999 Elsevier Science B.V. All rights reserved.