Development of high-performance frontal analysis and the application to the study of drug-plasma protein binding

Drug-plasma protein binding is a reversible and kinetically rapid interaction process which should be analyzed without disturbing the binding equilibrium. Till now, equilibrium dialysis and ultrafiltration followed by HPLC have been used to determine the unbound drug concentrations. However, this method involves problems such as drug adsorption onto the membrane and leakage of bound drug. Furthermore, the drug-protein binding equilibrium may deviate due to the change in sample concentration during filtration. To overcome these problems a novel chromatographic method, high-performance frontal analysis (HPFA), was developed. This article describes the principles of HPFA and its applicability to the study of stereoselective protein binding. (C) 1999 Elsevier Science B.V, All rights reserved.