Different retention behavior of structurally diverse basic and neutral drugs in immobilized artificial membrane and reversed-phase high performance liquid chromatography: comparison with octanol-water partitioning.

The retention behavior of 43 structurally diverse neutral and basic drugs in immobilized artificial membrane chromatography was investigated and compared to the reversed-phase retention and octanol-water partitioning. IAM chromatography was performed using morpholinepropanesulfonic acid (MOPS) or phosphate buffer saline (PBS) at pH 7.4 as the aqueous component of the mobile phase. The differences in the retention factors were attributed to increased electrostatic interactions in the MOPS environment, dependent on the fraction of charged species. Electrostatic interactions were found to play a key role in the relationships with reversed-phase retention factors determined under two different mobile phase conditions as well as in the relationships with lipophilicity data. IAM retention factors correlated better with octanol-water partition coefficients log P than with log D(7.4), as a result of the contribution of electrostatic forces in IAM retention. With log D(7.4) the relationships were improved when the fraction of charged species was taken into consideration. In any case the regression coefficient of log P or log D(7.4) was considerably lower than 1 reflecting the reduced hydrophobic environment of the IAM stationary phase. The different data sets were submitted to principal component analysis for further exploration of their similarities/dissimilarities.