Rapid Gradient RP-HPLC Method for Lipophilicity Determination: A Solvation Equation Based Comparison with Isocratic Methods

Abstract

The chromatographic hydrophobicity index (CHI) obtained from high-throughput gradient elution reversed-phase HPLC with ODS column and acetonitrile mobile phase has been shown to be well correlated with log k values obtained by isocratic elution in the same system; between CHI and log k50, the correlation coefficient was 0.99 for a very diverse set of 55 compounds. CHI and log k50 are moderately correlated with log P (water/octanol), and both can be used as alternative measures of lipophilicity. Analyses using the general solvation equation of Abraham shows that the solute factors that influence CHI and log k50 are not entirely the same as those that influence log P, so that neither CHI nor log k50 can be used as a direct measure of log P and vice versa. However, the factors that influence CHI are qualitatively and quantitatively the same as those that influence log k50, so that the rapidly determined CHI indexes encode exactly the same information as do isocratic log k values.