Liquid Chromatographic Estimation of Octanol/Water Partition Coefficients with a High Efficiency, Nonporous, Ultrasmall Particle Size Reverse Phase Stationary Phase

Abstract

HPLC retention data, obtained over a range of organic modifier fractions φ in binary mobile phases, can be used to estimate a compounds octanol/water partition coefficient (log P_o/w). Such a determination is facilitated by a high efficiency, low capacity column. The utility of a nonporous, ultrasmall particles size (1.5 μ), C₁₈ stationary phase capable of such performance was assessed using aqueous mobile phases containing either acetonitrile or methanol. In general, compounds were effectively eluted from this stationary phase at lower values of φ than with more typical stationary phases, thus increasing the accuracy and speed with which log K_w, the capacity factor in a 100% aqueous mobile phase, could be determined. Values of log K_w obtained for seventeen model compounds were highly correlated with the compound's log P_0/w. Comparison of retention trends in the methanol and acetonitrile mobile phases suggests differences in the retention mechanisms for both organic modifiers.