Prediction of human serum albumin-drug binding affinity without albumin

A new liquid chromatographic system was developed to measure protein-drug binding affinity indirectly without albumin and was evaluated using log nK values of drugs measured by a modified Hummel-Dreyer method using purified human serum albumin. The retention factors of acidic and basic drugs were measured by reversed-phase and ion-exchange liquid chromatography in sodium phosphate buffer, pH 7.40, containing 50 vol.% methanol at 37 degreesC. The bonded phases were pentyl, guanidino and carboxyl phases. The combined retention factors were correlated with the log nK values measured by a modified Hummel-Dreyer method because glycosylation of human serum albumin did not significantly affect log nK value. The correlation coefficients were 0.949 (n = 7) for acidic drugs and 0.978 (n = 5) for basic drugs. The log nK values of 26 acidic and 18 basic drugs were predicted from their retention factors measured by reversed-phase and ion-exchange liquid chromatography. (C) 2002 Elsevier Science B.V. All rights reserved.