DETERMINATION OF DISTRIBUTION COEFFICIENTS FOR SOME 5-HT3 RECEPTOR ANTAGONISTS BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

It is of major interest to determine the physico-chemical properties, dissociation constants and lipophilicity of potential drugs owing to t heir implication in absorption mechanisms. The HPLC capacity factors a ppear to be attractive and readily accessible lipophilic parameters. A n isocratic HPLC method was designed using a C-8 column to determine t he relative lipophilicity for two sets of 5-HT3 receptor antagonists, including tropine and quinolizine analogues. Dimethyloctylamine was ad ded to the eluent to mask silanophilic interactions and lead to a pred ominant partitioning mechanism. The capacity factors determined by a m onocratic procedure showed good correlations with the distribution coe fficients obtained by the shake-flask method, showing the validity of capacity factors as lipophilicity descriptors for close analogues.