ANALYTICAL AND PREPARATIVE RESOLUTION OF ENANTIOMERS OF VERAPAMIL AND NORVERAPAMIL USING A CELLULOSE-BASED CHIRAL STATIONARY-PHASE IN THE REVERSED-PHASE MODE

Analytical HPLC methods were developed for the chiral resolution of verapamil and norverapamil using a cellulose-based chiral stationary phase (Chiralcel OD) in the reversed-phase mode. The effect of pH, buffer concentration, and temperature on the analytical chiral separation were investigated. It was shown that retention decreased slightly with increasing pH, while alpha and resolution were unaffected by pH. Increasing buffer concentration from 0.01 to 0.125 M resulted in increased retention, while concentrations above 0.125 M resulted in decreased retention. Separation was unaffected by buffer concentration, while resolution increased with increasing buffer concentration. Maximum analytical resolution was obtained at subambient temperatures. Separation was unaffected by temperature, while an increase in temperature resulted in decreased retention. In addition, the preparative resolution of the enantiomers of verapamil and norverapamil was investigated. The analytical methods were scaled up to preparative loadings and the chromatographic parameters varied to determine their effect on the preparative separations.