Panagiotis Danias
National Technical University of Athens, Greece
Title: Retention behavior of structurally-diverse drugs on biopartitioning micellar chromatography and its potential to estimate cell permeability
Biography
Biography: Panagiotis Danias
Abstract
Biopartitioning micellar chromatography (BMC) utilizes micelles formed by a surfactant, such as polyoxyethylene (23) lauryl ether (Brij35), in a concentration higher than its critical micelle concentration and a reversed-phase stationary phase in order to gain insight into drug-membrane interactions, by rapid, friendly and reproducible measurements. The chromatographic column, modified by the surfactant, resembles the ordered array of the membranous hydrocarbon chains in regards to hydrophilic/hydrophobic character and the interactions of xenobiotics with the H-bonding groups of the adsorbed surfactant similar to the membrane ones. Therefore, the characteristics of the BMC are similar to biological barriers. Up to now, the reported studies of BMC to model toxicity (LD50), blood-brain barrier penetration, plasma clearance, volume of distribution as well as oral absorption are based on limited datasets and therefore, further investigations are needed. The aim of the present study was the evaluation of the potential of biopartitioning micellar chromatography to estimate cell permeability. For this purpose, retention indices (logkw) of an extended set of structurally-diverse drugs were measured on a discovery RP- 18 column using as eluent phosphate buffer in the presence of Brij at a concentration of 0.04 M. The effect of the addition of NaCl in a concentration of 9.2 g/L was studied as well as the effect of increase of temperature from ambient to 37oC. Retention factors were compared with octanol-water partitioning and retention factors obtained in immobilized artificial membrane (IAM) chromatography. Retention factors were subsequently compared with Madin Darby Canine Kidney (MDCK) cell lines permeability data taken from literature and they were used to model % Human Oral Absorption (% HOA) data, compiled from literature sources. For reasons of comparison, the constructed models were compared with those derived by octanol-water partitioning.