Chiral chromatography method screening strategies: Past, present and future

Method screening is an integral part of chromatographic method development for the separation of racemates. Due to the highly complex retention mechanism of a chiral stationary-phase, it is often difficult, if not impossible, to device predefined method-development steps that can be successfully applied to a wide group of molecules. The standard approach is to evaluate or screen a series of stationary and mobile-phase combinations to increase the chances of detecting a suitable separation condition. Such a process is often the rate-limiting step for high-throughput analyses and purification workflows. To address the problem, several solutions and strategies have been proposed over the years for reduction of net method-screening time. Some of the strategies have been adopted in practice while others remained confined in the literature. The main objective of this review is to revisit, critically discuss and compile the solutions published over the last two decades. We expect that making the diverse set of solutions available in a single document will help assessing the adequacy of existing screening protocols in laboratories conducting chiral separation.