Enantioseparation of angiotensin II receptor type 1 blockers: evaluation of 6-substituted carbamoyl benzimidazoles on immobilized polysaccharide-based chiral stationary phases. Unusual temperature behavior

•Separation of 6-substituted carbamoyl benzimidazoles with a chiral center on immobilized polysaccharide-based CSPs.•Mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes.•Thermodynamic parameters were calculated at constant mobile phase compositions in the temperature range 10-35 °C.•Unusual temperature behavior was observed on Chiralpak IC: retention factor increased with increasing temperature.•Tiso was as high as several thousand degrees centigrade.

Enantioseparation of thirteen 6-substituted carbamoyl benzimidazoles by high-performance liquid chromatography (HPLC) was investigated using two immobilized polysaccharide-based chiral stationary phases (CSPs), Chiralpak IC and Chiralpak IA, in normal-phase mode. Most of the examined compounds were completely resolved. The effects of a polar alcohol modifier, analyte structure, and column temperature on the chiral recognition were investigated. Furthermore, the structure-retention relationship was evaluated, and thermodynamic parameters were calculated from plots of ln k′ or ln α versus 1/T. The thermodynamic parameters indicated that the separations were enthalpy-driven. Moreover, nonlinear van't Hoff plots were obtained on Chiralpak IA. However, two unusual phenomena were observed: (1) an unusual increase in retention with increasing temperature with linear van't Hoff plots on Chiralpak IC and (2) an extremely high Tiso value (i.e., several thousand degrees centigrade).