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).