Immobilized artificial membrane chromatography : quantitative structure-retention relationships of structurally diverse drugs

The chromatographic capacity factors (log k‘) for 32 structurally diverse drugs were determined by high performance liquid chromatography (HPLC) on a stationary phase composed of phospholipids, the so-called immobilized artificial membrane (IAM). In addition, quantitative structure-retention relationships (QSRR) were developed in order to explain the dependence of retention on the chemical structure of the neutral, acidic, and basic drugs considered in this study. The obtained retention data were modeled by means of multiple regression analysis (MLR) and partial least squares (PLS) techniques. The structures of the compounds under study were characterized by means of calculated physicochemical properties and several nonempirical descriptors. For the carboxylic compounds included in the analysis, the obtained results suggest that the IAM-retention is governed by hydrophobicity factors followed by electronic effects due to polarizability in second place. Further, from the analysis of the results obtained of two developed quantitative structure-permeability studies for 20 miscellaneous carboxylic compounds, it may be concluded that the balance between polarizability and hydrophobic effects is not the same toward IAM phases and biological membranes. These results suggest that the IAM phases could not be a suitable model in assessing the acid-membrane interactions. However, it is not possible to generalize this observation, and further work in this area needs to be done to obtain a full understanding of the partitioning of carboxylic compounds in biological membranes. For the non-carboxylic compounds included in the analysis, this work shows that the hydrophobic factors are of prime importance for the IAM-retention of these compounds, while the specific polar interactions, such as electron pair donor−acceptor interactions and electrostatic interactions, are also involved, but they are not dominant.