Misconceptions about chromatography mean that the technology is rarely considered as a means to isolate pure enantiomers at production scale. Aline Devoille, Novasep, argues that it is time for a rethink.
Preparative chiral chromatography is not only highly reproducible but also robust, cost-effective, straightforward to scale up, and eco-friendly. As chemical APIs become increasingly complex, often containing two or more chiral centres, there is a growing need for advanced purification technologies to reach the required chemical but also enantiomeric purity. In this context, chromatography is a solution of choice for chiral resolutions.
Several options are available to resolve chiral mixtures at large scale, among which three preparative chromatography technologies are highly competitive: High Performance Liquid Chromatography (HPLC), Supercritical Fluid Chromatography (SFC) and Multi-column Continuous Chromatography (MCC). In all three cases, the chromatography column is filled with a chiral stationary phase (CSP) selected after screening of commercially available ones. The critical choice of a chromatography technology for a given purification often depends on the product development stage and on the scale at which the separation is to be carried out (see Figure 1).