Determination of alkane/water partition coefficients of polar compounds using hydrophilic interaction chromatography

In this study, the retention factors (log k) of 44 polar neutral compounds were measured using hydrophilic interaction chromatography (HILIC). This retention parameter was compared with experimental log Palk obtained by a traditional method (shake-flask) or with the calculated log Palk for the most hydrophilic compounds. A good correlation was obtained between log k90 (measured with a mobile phase containing 90% acetonitrile) and log Palk. In contrast, no correlation was obtained between the retention factor and log Poct. This method could thus represent an advantageous alternative and reliable method to characterise the lipophilicity of polar compounds in an alkane/water system by chromatography, providing an important insight in (Q)SAR studies to predict drug permeation through numerous biorelevant membranes.

► log k obtained on HILIC and calculated or published log Palk were compared. ► Mobile phase containing 90/10 (v/v) acetonitrile/water was used. ► Influence of solute structural properties on log Palk and log kHILIC is similar. ► HILIC can be used to assess water/alkane partition coefficients of polar compounds. ► This is the unique HTS approach to assess such log P.