2002 Volume 50 Issue 12 Pages 1578-1583
The use of log k derived from reversed phase (RP)-HPLC retention times provides a convenient method for estimating log Poct values (Poct: 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 Poct in accord with our earlier proposal that use of log kM50 provides a convenient means for rapid estimation and prediction of log Poct.
