Hydrophobicity parameters determined by reversed-phase liquid chromatography. XV: Optimal conditions for prediction of log Poct by using RP-HPLC procedures

Abstract

The use of log k derived from reversed phase (RP)-HPLC retention times provides a convenient method for estimating log Poct values (P oct: 1-octanol/water partition coefficient). In order to establish optimal HPLC conditions, the difference between chromatographic (C18 modified column and aqueous methanol eluents) and bulk solvent systems was examined by use of a batch-like equilibration with octane/aqueous methanol. Comparison of values for log PO/M-W (log P for the Octane/MeOH-Water partitioning system) and log k measured for monosubstituted pyrazines at different methanol concentrations, showed closest correlation (r, 0.94) with 50% aqueous methanol; and importantly, under these conditions, log k shows even better correlation (r, 0.99) with log Poct. Effects of residual silanols on HPLC retention with C18 stationary phases were examined. The results show that, in the presence of a small quantity of accessible silanols, the use of 50% aqueous methanol (M50) as eluent yields values of log k directly proportional to log P oct in accord with our earlier proposal that use of log k M50 provides a convenient means for rapid estimation and prediction of log Poct. © 2002 Pharmaceutical Society of Japan.