Retention-activity relationship studies of benzodiazepines by micellar liquid chromatography

Solute partitioning into lipid bilayers of biological membranes is the basis for drug and metabolite uptake, passive transport across membranes and bioaccumulation. In order to emulate in vitro the partitioning process in the biomembranes, different approaches have been proposed. The use of micellar solutions as mobile phases in reversed-phase liquid chromatography (micellar liquid chromatography, MLC) has proven to be valid in the prediction of the biological activities of local anesthetics, catecholamines and barbiturates. In this paper we focus our attention on benzodiazepines. The retention of benzodiazepines using different concentrations of Brij35 as micellar mobile phase in modified C(18) stationary phase was studied. Quantitative retention-activity relationships (QRAR) in MLC were investigated for these compounds. An adequate correlation between the capacity factors (log k) and the toxicity (log LD(50)) and anxiolitic activity (log ED(50)) of benzodiazepines was obtained.