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

The method to predict 1-octanol-water partition coefficients (K-ow) fr om capacity factors (k') obtained by Reversed-Phase High-Performance L iquid Chromatography (RP-HPLC) has been extended to use gradient eluti on rather than isocratic elution. The mobile phase has been changed ei ther linearly or exponentially with time. The initial composition of t he mobile phase and its rate of change affected the log K-ow versus lo g k' relation. This relation was exponential in linear gradient experi ments. For non-linear gradient elution in which the water fraction of the mobile phase decreased exponentially from 100% to approach 0% asym ptotically, a physically-based equation describing the dependence of l og K-ow on log k' has been derived. Without any preliminary estimation , RP-HPLC gradient elution allows a precise prediction of log K-ow ove r a range of nearly six orders of magnitude.