PREDICTING 1-OCTANOL-WATER PARTITION-COEFFICIENT BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY GRADIENT ELUTION

The method to predict 1-octanol-water partition coefficients (K-ow) from capacity factors (k') obtained by Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) has been extended to use gradient elution rather than isocratic elution. The mobile phase has been changed either linearly or exponentially with time. The initial composition of the mobile phase and its rate of change affected the log K-ow versus log k' relation. This relation was exponential in linear gradient experiments. For non-linear gradient elution in which the water fraction of the mobile phase decreased exponentially from 100% to approach 0% asymptotically, a physically-based equation describing the dependence of log K-ow on log k' has been derived. Without any preliminary estimation, RP-HPLC gradient elution allows a precise prediction of log K-ow over a range of nearly six orders of magnitude.