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

摘要

The chromatographic hydrophobicity index (CHI) ob-mined from high-throughput gradient elution reversedphase 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 k↓(50), the correlation coefficient was 0.99 for a very diverse set of 55 compounds. CHI and log k↓(50) 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 k↓(50) are not entirely the same as those that influence log P, so that neither CHI nor log k↓(50) 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 k↓(50), so that the rapidly determined CHI indexes encode exactly the same information as do isocratic log k values.