Joint use of cyclodextrin additives in chiral discrimination by reversed-phase high-performance liquid chromatography: temperature effects

The temperature dependence of chiral separations was investigated in combin ed system of reversed-phase (RP) Liquid chromatography using two chiral add itives: single alpha or beta native cyclodextrins and their permethylated d erivatives. The model tested compounds of pharmaceutical interest were: met hylphenobarbital, mephenytoin, morsuximide and camphor. Taking the localiza tion of a complexation process as a criterion - the combined system with tw o selectors has been rationalized as occurring in three stages. The influen ce of temperature (in narrow range of 20 degrees C) on retention and enanti oselectivity was studied in; System I (complexation occurs in the mobile ph ase), in System II (complexation on the stationary phase) and in System III (complexation in both phases together). In System III (as for System I) it has been found that the model compounds could be classified into three gro ups based on their retention dependence on temperature: retention decrease with temperature decrease, retention increase with temperature decrease or no influence of temperature on retention. For all the compounds investigate d, decrease in temperature increases the selectivity. Standard enthalpy (De lta H-0) and entropy (Delta S-0) changes of solute transfer between the mob ile and the stationary phase and standard enthalpy (Delta H-CD(0)) and entr opy (Delta S-CD(0)) changes of complex formation were also calculated. In S ystems I and III, if the complexation in the mobile phase is favored proces s compared with interaction with the stationary phases (RP or covered by pe rmethylated cyclodextrin), the shortest retention time and the best selecti vity is observed at low temperature. (C) 1999 Elsevier Science B.V. All rig hts reserved.