AbstractAn optical resolution of the amide derivatives of ibuprofen and the carbamate‐alkylester derivatives of thetrans‐alcohol metabolite of loxoprofen and an analogous compound, CS‐670, was studied by chiral high‐performance liquid chromatography (HPLC). The chiral columns SUMIPAX OA‐4000 and OA‐4100 were used to investigate the enantiomeric separation behavior of these derivatives using both reversed and normal mobile phases. A better separation factor (α) of the amide and the carbamate ester derivatives was obtained in the normal mobile phase than in the reversed mobile phase HPLC. In addition, the recognition mechanisms of both amide and carbamate ester enantiomers were investigated by1H‐nuclear magnetic resonance (NMR). It is suggested that the important driving forces for the enantiomeric separation are the formation of hydrogen bonding and the charge transfer complex between these derivatives and an active site of the chiral stationary phase. © 1995