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

Abstract

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 Po/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 Kw, the capacity factor in a 100% aqueous mobile phase, could be determined. Values of log Kw obtained for seventeen model compounds were highly correlated with the compound's log P0/w. Comparison of retention trends in the methanol and acetonitrile mobile phases suggests differences in the retention mechanisms for both organic modifiers.