Retention-activity relationship studies of benzodiazepines by micellar liquid chromatography

Solute partitioning into lipid bilayers of biological membranes is the basi s for drug and metabolite uptake, passive transport across membranes and bi oaccumulation. In order to emulate in. vitro the partitioning process in th e biomembranes, different approaches have been proposed. The use of micella r solutions as mobile phases in reversed-phase liquid chromatography (micel lar liquid chromatography, MLC) has proven to be valid in the prediction of the biological activities of local anesthetics, catecholamines and barbitu rates. In this paper we focus our attention on benzodiazepines. The retenti on of benzodiazepines using different concentrations of Brij35 as micellar mobile phase in modified C-18 stationary phase was studied. Quantitative re tention-activity relationships (QRAR) in MLC were investigated for these co mpounds. An adequate correlation between the capacity factors (log k) and t he toxicity (log LD50) and anxiolitic activity (log ED50) Of benzodiazepine s was obtained. Copyright (C) 1999 John Wiley & Sons.