Accurate determination of log k'w in reversed-phase liquid chromatography. Implications for quantitative structure-retention relationships.

With increased understanding of the retention mechanisms of reversed-phase LC has come increased usage of the technique for the measurement of physico-chemical data, especially partitioning information that can be used for quantitative structure-activity relationships. However, the use of chromatographic retention requires that a standard set of mobile phase conditions be chosen. The choice of 100% water has theoretical advantages, as an aqueous phase-membrane phase is the most common system being modeled. However, experimental measurement of k' values with this mobile phase is difficult or impossible for most real solutes. Various retention extrapolation methods to 100% water have been proposed, but when compared, often yield different values for the same solute. Most of the extrapolation methods are based on the retention as a function of the mobile phase only. However, as the retention is controlled by solute partitioning between the mobile phase and stationary phase, stationary phase effects cannot be ignored. In this paper log k'w values extrapolated from different methods are compared to the measured values. Prediction of log k'w is attempted from the retention as a function of both the mobile phase and stationary phase. Solvatochromic analysis is used to deconvolute stationary and mobile phase effects. Log k'w values extrapolated from ET(30) plots are recommended as the most meaningful representation of retention for quantitative structure-retention relationships.