Alternatives to chiral LC

LC is undoubtedly the most important technique in the chiral analysis of pharmaceuticals. However, that is not to say that chiral LC of pharmaceuticals is synonomous with chiral analysis of pharmaceuticals. The chiral selectors utilised in LC may be usefully deployed in a range of other analytical techniques. Despite this, chiral LC is more dominant now than it ever was. The early commercial developments in chiral analysis were in LC. The application of similar selector systems was demonstrated in other techniques but now with the notable exception of chiral capillary electrophoresis (CE) there is a strong reliance again on LC. 

Chiral GC was under development and was being used successfully, for example for chiral dmg bioanalysis, at the same time as commercialised CSP for LC were breaking through. The technique received a boost when cyclodextrin GC phases came onto the market. However, with most drug bioanalysis being carried out by LC, and LC-MS in particular, chiral GC is more the preserve of application areas such as the analysis of odourous compounds [24] and the field of insect pheromones [25]. 

In chiral CE, screening approaches can be so facile that there is often little need for a rational approach. Just how successful CE screening can be may be gauged by studying the work of Nussbaum [26] who used a screen involving five cyclodextrins, each at a high or low concentration, and 

This limitation applies even more so to chiral capillary electrochromatography (CEC). This technique [27] is essentially LC in a fused silica capillary using an electric field rather than a pressure drop to drive the flow. As such the separations may be achieved by chiral derivatisation, by use of a CMPA or a CSP 

Both CE and CEC would stand a better chance if the tendency to reduce dimensions in LC had progressed to the point where the standard LC column was at least of 1 mm i.d. and could be used in a system that was also compatible with running CE and CEC. Such a hybrid system has existed as a prototype but was probably ahead of its time. 

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The technology alternative to chiral LC is supercritical fluid chromatography (SFC) (Liu et al., 2002 Mangelings and Vander Heyden, 2008a, 2008b). SFC is essentially an NP format where CO2 is substituted for hexane. Gradients work well with SFC and usually span 5—50% B (alcohol) and facilitates fast method development. The combination of gradient and low viscosity often facilitates fast separations (usually at least three times faster than NP-LC). SFC works when combined with MS detection, but historically has not been easy to perform and has not worked as well as RP-LC/MS (White and Burnett, 2005). 

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