General Approach for the Estimation of Octanol/Water Partition Coefficient by Reversed-Phase High-Performance Liquid Chromatography

Abstract

General approach for the relation of reversed-phase high-performance liquid chromatographic retention behaviour to the hydrophobic properties of drugs was developed. Hydrophobicity of compounds was characterized by the logarithm of 1-octanol/water partition coefficient (log P_o/w). Reversed-phase retention times of 26 model compounds (log P_o/w values of them ranged from −1.22 to 3.84) were measured using 3 to 5 different mixture of acetonitrile and water as eluent and the logarithm of the capacity ratios (log k′) was calculated. The linear relationship between the log k′ values and the percentage of the acetonitrile in the eluent was tested for each molecule. The slope and the intercept (log k′_o) of these straight lines were calculated and introduced to the following regression equation: a, b and c, were constants obtained by least squares method. Correlation coefficient of the equation was 0.95. The quotient of the values of a and b gave the percentage of the acetonitrile in the eluent (48%) by which the chromatographic partition system became the best model of the 1-octanol/water partition system. The proposed method provides the possibility of estimating log P_o/w values for compounds which can not be eluted by one isocratic eluent composition.