Preparative chiral separations on cyclodextrin silica stationary phases

Abstract

Due to the fact that the enantiomers of chiral pharmaceuticals have different pharmacological effects, it is necessary to perform pharmacological studies on the enantiomers separately. For this to be possible, methods for separating preparative amounts of the enantiomers must be available. The cyclodextrin silica based stationary phases designed for HPLC are commercially available and offer unique selectivity for a significant number of chiral compounds. However, their use for preparative separations is limited by low chiral selectivity values, low loadability and low efficiency. Currently, because there is insufficient data for making a quantitative comparison between the displacement mode and the elution mode, there is disagreement as to which preparative separation method provides higher production rates and higher per cent recovery of the loaded material. This dissertation describes the development of preparative chromatographic separations in both the displacement mode and the overloaded elution mode for a number of chiral compounds (many of which are of interest to the pharmaceutical community) on three commercially available CD stationary phases. The results of the two methods are compared with regard to production rates and per cent recoveries. It also investigates the differences which exist between the two methods with respect to the purification and collection of the less retained and the more retained enantiomer.