Liquid Chromatographic Separation and Thermodynamic Investigation of Ethyl Nipecotate Enantiomers on Immobilized Amylose-Based Chiral Stationary Phase

Ethyl nipecotate enantiomers are widely used as chiral building blocks in the synthesis of drug substances. An efficient and economic chiral high-performance liquid chromatographic method for determination of enantiomeric purity of ethyl nipecotate is developed and validated. Chiral separation was achieved on immobilized amylose-based stationary phase using a mixture of n-hexane: ethanol: diethylamine (80:20:0.1, v/v/v) as mobile phase. Resolution between R-(-)-ethyl nipecotate (REN) and S-(+)-ethyl nipecotate (SEN) peaks was found to be 3.59. The detector response of SEN exhibited an excellent linearity over the concentration range of 4.5-120 mu g mL(-1). The limit of detection and limit of quantification for SEN were 0.016 and 0.045 mu g and REN were 0.015 and 0.043 mu g, respectively. The influence of column oven temperatures on chiral retention and separation was studied in the range of 25 degrees C to 50 degrees C; the thermodynamic parameters Delta H degrees, Delta S degrees and Delta G degrees were evaluated from van't Hoff plots and used to explain the strength of interaction between analyte and stationary phase.