Chiral drug separation techniques

Enantiomers are distinguished on the basis of their interaction with a chiral selector. Development of chiral selectors or chiral stationary phases (CSPs) for GC, HPLC, and CE has rapidly opened a new dimension in the area of chiral drug separation techniques. There are different chiral selectors available for enantiomeric separation of drugs and pharmaceuticals. Finding a suitable chiral selector, whether immobilized on a solid support (GC, HPLC) or added to a running buffer (HPLC, CE), is still often based on trial and error. A few predictions can be made, however, if common structural elements are present. After a selector has been chosen, variables, such as the nature, ionic strength, and pH of buffer, can be varied, as can presence of organic modifiers, temperature, and so on. 

The main methods used for chiral drug separation are GC, HPLC, and Other techniques, such as... 

Chiral Drug Separation Table 3 Differences between HPLC and CE as chiral separation techniques 457... 

Capillary electrophoresis offers a set of important advantages that make it a premier technique for the investigation of enantioselective effects in the affinity interactions between chiral drugs and cyclodextrins. The most important advantage of CE is the inherently high separation efficiency offered by this technique. As already known, the most important contributors to peak resolution (R) are a separation selectivity (a) and an efficiency (N). A relationship between these parameters in CE is described by the following equation (2) ... 

Thus, as shown earlier, CE represents a suitable technique for the determination of enantioselective binding constants between chiral drugs and cyclodextrins. The results obtained under appropriate conditions are reasonable and can be applied for optimization purposes as well as for a better understanding of the fine nuances of chiral CE separations. On the other hand, some care must be taken for the proper application of CE methods for the determination of the binding constants as well as when applying these data. A critical review of the calculation of stability constants for the chiral selector-enantiomer interactions from electrophoretic mobilities has been published by Vespalec and Bocek (40). 

In studies of a chiral drug candidate and its possible metabolites in preclinical and clinical Phase I to Phase III, most of the biological sample matrices, such as urine, plasma, serum, saliva, cerebrospinal fluid, and tissue homogenates, are more compatible with CE than chromatographic techniques. Moreover, it is not possible in GC and difficult in chiral HPLC to achieve the chiral separation of a drug and its phase I and phase II metabolites in a single run. By contrast, this is possible with chiral CE, as in the simultaneous chiral separation of Phase I and Phase II metabolites of chiral antihistaminic drug dimethindene. ... 

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