Review articlePreparative supercritical fluid chromatography: A powerful tool for chiral separations

•Survey of the recent publications in the field of preparative scale.•Major millestones of the SFC development.•Review focuses on pharmaceutical compounds, where chirality is of utmost importance.•In preparative purpose polysaccharide and Pirkle CSPs are the most used.•In preparative area, SFC is the method of choice because of its green advantages.

In 2012, the 4 biggest pharmaceutical blockbusters were pure enantiomers and separating racemic mixtures is now frequently a key step in the development of a new drug. For a long time, preparative liquid chromatography was the technique of choice for the separation of chiral compounds either during the drug discovery process to get up to a hundred grams of a pure enantiomer or during the clinical trial phases needing kilograms of material. However the advent of supercritical Fluid Chromatography (SFC) in the 1990s has changed things. Indeed, the use of carbon dioxide as the mobile phase in SFC offers many advantages including high flow rate, short equilibration time as well as low solvent consumption. Despite some initial teething troubles, SFC is becoming the primary method for preparative chiral chromatography. This article will cover recent developments in preparative SFC for the separation of enantiomers, reviewing several aspects such as instrumentation, chiral stationary phases, mobile phases or purely preparative considerations including overloading, productivity or large scale chromatography.