Rate constant determination of interconverting enantiomers by chiral chromatography using a stochastic model

Abstract

It may happen under the conditions employed that enantiomers interconvert to each other. In this case, obviously, the kinetics of the process is to be examined. When enantiomers dynamically interconvert to each other during the separation process, a plateau is observed between the adjacent peaks (so-called Batman peak appears). The peak shape depends on the rate constant of this dynamic reaction.A novel stochastic model was derived which takes both the separation and the interconversion into account at the molecular level – thus the effects of the parameters affecting the separation can be investigated. The novel model was used for the study of quetiapine, a drug molecule that interconverts during the separation to evaluate the rate constant based on the enantiomerization. Various flow rates and temperatures were used, and good agreement was obtained with the rate constant obtained from optical rotation experiments and with the software written by Trapp [1]. The most important result we concluded is the need of mild conditions during the separation to ascertain the rate constant the most accurately (low flow rates and temperatures where the enantiomerization process is limited to a few interconversions). The comparison of the rate constants of the on-column and the off-column experiments should be done by considering the stationary phase effects that are absent in the off-column experiments.