Enantioseparation of Chiral Drugs – An Overview

The belief that pure single enantiomers would provide safer and more effective alternatives to racemates, has resulted in a greater stress on the evaluation and development of single isomers as drug products. Almost half of the drugs in use today are chiral. It is well established that the pharmacological activity is mostly restricted to one of the enantiomers and the individual enantiomers of racemic drugs frequently differ in their biological effects. In many cases, the inactive enantiomer shows unwanted side effects or even toxic effects. For pharmacological studies of such drugs, there is, therefore a need for an effective means of separating and quantifying the enantiomers in biological samples. The chiral switch process (racemate to single enantiomer ) has resulted in a number of agents being re-marketed as single enantiomer products. Analytical methods which have been used for enantioseparation, include diastereomeric crystallization, biocatalysis , chromatographic techniques [thin layer chromatography, gas chromatography, superand sub-critical fluid chromatography, nano-LC, high-performance liquid chromatography] , affinity electrokinetic chromatography, electromigration techniques [capillary electrophoresis (CE: CZE, MEKC, MEEKC) and capillary electrochromatography (CEC)]. The application of nanoparticles or nanostructured materials to enantioseparation has been recently described. Multimodal HPLC screening of polysaccharide-based CSPs enabled the rapid and successful enantioseparation of a large number of chiral drugs.The existing commercial projects have demonstrated that it is often cheaper to produce single enantiomeric drugs with chromatography rather than use traditional technologies such as crystallization and/or asymmetric synthesis. Recent achievements in enantioseparation of chiral drugs have ben reported. The success of chiral separation achieved by CE has been extended to microfabricated electrophoresis devices. Coupling electromigration techniques with MS have already been shown to be means for improving detection sensitivity. Optimization of the separation is still not quite understood and further research in this direction is required.