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 interacti on process which should be analyzed without disturbing the binding equilibr ium. Till now, equilibrium dialysis and ultrafiltration followed by HPLC ha ve been used to determine the unbound drug concentrations. However, this me thod involves problems such as drug adsorption onto the membrane and leakag e of bound drug. Furthermore, the drug-protein binding equilibrium may devi ate due to the change in sample concentration during filtration. To overcom e these problems a novel chromatographic method, high-performance frontal a nalysis (HPFA), was developed. This article describes the principles of HPF A and its applicability to the study of stereoselective protein binding. (C ) 1999 Elsevier Science B.V, All rights reserved.