Novel RPLC stationary phases for lipophilicity measurement: Solvatochromic analysis of retention mechanisms for neutral and basic compounds

An RPLC was developed to rapidly determine lipophilicity of neutral and basic compounds using three base deactivated RPLC stationary phases particularly designed for the analysis of basic compounds, namely, Supelcosil ABZ + Plus, Discovery RP Amide C 16 , and Zorbax Extend C 18 . The work consisted of three sets of experiments. In the first log k   w values of neutral compounds were extrapolated using hydroorganic mobile phases at different compositions. Good correlation between log k   w and log P oct indicated that the method was appropriate for these supports, without adding a silanol masking agent. In the second set of experiments, isocratic log k values of neutral and basic compounds were measured with three different mobile phases. The best estimation of lipophilicity was obtained for neutral and basic compounds when the secondary interactions were strongly reduced ( i. e. , when basic compounds were under their neutral form). In the third set of experiments, isocratic retention factors of basic compounds (in their neutral form) were measured with a high‐pH mobile phase, on a chemically stable support (Zorbax Extend C 18 ). Under these chromatographic conditions, correlation between the isocratic retention factors and log P oct (log D   10.5 ) for basic compounds was similar to that for neutral compounds.