Analytical Chemistry · 1998 · 132 citations · 13 references
PharmacyChemistryPharmaceutical AnalysisAnalytical ChemistryChromatographic AnalysisMass Spectrometric AnalysisAnalytical ChromatographyChromatographyGradient ElutionLiquid ChromatographyHydrophobicityHydrophobicity EffectsIsocratic Method ValidationLipophilicity PredictionLog P DeterminationMobile Phase EffectsMolecular LipophilicityReversed-phase Gradient Elution
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 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.
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