Use of liquid chromatography and theoretical computational methods to compare the lipophilicity of selected cortisone derivatives

Abstract

Selected cortisone derivatives (corticosterone acetate, 11-dehydrocorticosterone acetate, corticosterone, 11-dehydrocorticosterone, allo-dihydrocortisone, hydrocortisone, and cortisone) have been separated by reversed-phase thin-layer chromatography and reversed-phase high-performance liquid chromatography. Experimental partition coefficients (log Pexp ) of the derivatives were determined for the n -octanol-water system. Chromatographic data ( RF , RM , tR , and log k ) were correlated with experimental (log Pexp ) and with theoretical n -octanol-water partition coefficients ( A log PS , IA log P , log PKowwin , x log P , C log P , mi log P , log PRekker ) and with the hydrophilic-lipophilic balance ( HLB ) of the compounds. It was found that corticosterone acetate should have the highest lipophilicity whereas cortisone should have the lowest. It was found that the chromatographic retention data ( RF , RM , tR , and log k ) correlated best with mi log P and x log P . Because the experimental values (log Pexp ) of all the cortisone derivatives investigated were closest to mi log P values ( r = 0.9915) we conclude that mi log P is the best theoretical partition coefficient for evaluation of the lipophilicity of these cortisone derivatives.