Evaluation of experimental strategies for the development of chiral chromatographic methods based on diastereomer formation.

The past two decades has seen explosive growth in the field of chirality as illustrated by the rapid progress in the various facets of this intriguing field. Firstly, it is the basic understanding of the importance of chirality and, secondly, the awareness of the therapeutic pitfalls due to failure to recognize chirality that have paved the way for a rejuvenated interest in the field. Needless to say that the impetus for chiral separation advancement and enhancement has been found to be the highest in the past decade and still continues to be an area of high focus. In this regard, both direct and indirect separation approaches have been instrumental in placing into literature stereoselective pharmacokinetic and pharmacodynamic data of plethora of drug racemates. Also, today, the cloud of uncertainty associated with the development of a chiral molecule is a thing of the past because the field is so evolved and numerous options are available for stereoselective analysis. However, the decision to advance either a single enantiomer or a racemate for development has to be made by a rational approach with adequate justification. Although indirect method of chiral separation has been well established with numerous examples of well-documented cases of stereoselective pharmacokinetic data, there is a growing need for a review that provides a strategic overview of considerations and key issues for developing chromatographic methods based on diastereomer formation. This review provides a general framework for the exploratory planning and a definitive game plan for the establishment of chiral methods based on diastereomer formation. Also, it provides an exhaustive list of applications of numerous chiral derivatization reagents that have been used in the generation of stereoselective pharmacokinetic data. Copyright 2004 John Wiley & Sons, Ltd.