Prediction of the -Octanol/Water Partition Coefficients of Basic Compounds Using Multi-Parameter QSRR Models Based on IS-RPLC Retention Behavior in a Wide pH Range.

The -octanol-water partition coefficient (log) is an important physicochemical parameter which describes the behavior of organic compounds. In this work, the apparent -octanol/water partition coefficients (log) of basic compounds were determined using ion-suppression reversed-phase liquid chromatography (IS-RPLC) on a silica-based C18 column. The quantitative structure-retention relationship (QSRR) models between log and log (logarithm of retention factor corresponding to 100% aqueous fraction of mobile phase) were established at pH 7.0-10.0. It was found that log had a poor linear correlation with log at pH 7.0 and pH 8.0 when strongly ionized compounds were included in the model compounds. However, the linearity of the QSRR model was significantly improved, especially at pH 7.0, when molecular structure parameters such as electrostatic charge and hydrogen bonding parameters A and B were introduced. External validation experiments further confirmed that the multi-parameter models could accurately predict the log value of basic compounds not only under strong alkaline conditions, but also under weak alkaline and even neutral conditions. The log values of basic sample compounds were predicted based on the multi-parameter QSRR models. Compared with previous work, the findings of this study extended the pH range for the determination of the log values of basic compounds, providing an optional mild pH for IS-RPLC experiments.