Chiral drug separation importance

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) ... 

The importance of this mode of separation lies in the shear scale of the market for optically pure molecules. The sales of single enantiomer chiral drugs is currently U 180 billion per annum and —65% of active pharmaceutical ingredients (APIs) currently in development have at least one chiral centre. Apart... 

Separation of optically active isomers is one of the most important areas of HPLC apphcation in the pharmaceutical industry. Since most of biological systems are predominantly homochiral, different enantiomers of the same drug could have different effect and potency, and the development of enan-tioselective analytical (and preparative) separation methods is very important. Detailed description of chiral HPLC separation is given in Chapter 22 of this book here we only briefly review the specifics of distinctive types of chiral stationary phases (CSP). 

If a chiral drug could be sold as a single active enantiomer, it should be possible to use smaller doses with fewer side effects. Many chiral drugs continue to be sold as racemic mixtures, however, because it is more difficult and therefore more costly to obtain a single enantiomer. An enantiomer is not easily separated from a racemic mixture because the two enantiomers have the same physical properties. In Chapter 12 we will study a reaction that can form a single active enantiomer, an important development in making chiral drugs more readily available. 

Another important application of CDs is (chiral) drug analysis. In this field, CDs are used in combination with UV-VIS spectrometry, fluorescence and NMR spectroscopy, mass spectrometry, in electrochemical analysis and most widely in various separation techniques such as thin-layer chromatography (TLC), gas chromatograpy (GC), high-performance liquid chromatography (HPLC), super- and subcritical fluid chromatography (SFC) [13] and capillary electrophoresis (CE) [9], [16]. 

Harmonization of requirements has successfully been made by the International Conference on Harmonisation (ICH), e.g., in guidelines on stability documentation, method validation, and investigation of impurities. Regarding impurities information is given on how the limits should be set and at what level identification is needed. Similar efforts are seen for dissolution testing and how to correlate in vivo and in vitro data. The question of bioavailability and bioequivalence is an important one and has been dealt with as well. As a consequence of the rapid development in chiral separations we can now see a harmonization of requirements also for chiral drugs. 

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