ABSTRACT
While SFC found a niche in the petrochemical industry where nonpolar aromatics are of interest, the relatively polar nature of pharmaceuticals limited their ability to be analyzed by SFC. The earlier excitement of SFC fizzled. Instead, as a capillary chromatography technique, SFC was challenged by its inability to solvate enough polar molecules to maintain the attention of the chemical industry as a whole, and the pharmaceutical industry in particular. Primarily through the efforts of Berger [1], SFC evolved into a packed column technique that found a niche in preparative and chiral analysis. Before SFC could make strides in achiral analysis, SFC was essentially sidetracked as a technique for effective impurity discrimination by the Ultra High Performance Liquid Chromatography (UHPLC) revolution. Today’s SFC has had a rocky road to get here. As we will see in this text, traversing this path has been worth it. Although still today SFC has yet to match the advanced levels projected in the 1980s, it has established itself as a valuable chromatographic separation tool in the pharmaceutical analytical chemist’s toolbox. The introduction of traditional LC column format for packed column SFC eliminated the difficulties many laboratories had in running capillary SFC. The advent of chiral column chromatography created the demand for efficient normal phase separations. SFC is now the stalwart technique in preparative-scale chiral chromatography and is rapidly becoming the technique of choice for routine analytical applications of chiral chromatography as well. Since nearly 40% of drugs in use are known to be chiral and approximately a quarter of these are administered as pure enantiomers, SFC is involved in a substantial analytical and preparative market. Today’s SFC instrumentation enables the analytical chemist to develop highly efficient chromatographic methods and fast reequilibration. The dynamics of a supercritical fluid mobile phase enables chromatographic coupling and ease in interfacing with mass spectrometric (MS) detection. Preparative SFC has proven to significantly reduce development costs, minimize waste handling, and replace alkane solvents in many laboratories. Since SFC adds no additional carbon dioxide to the atmosphere, it is designated as a “green” analytical technique. It has several proven advantages over traditional HPLC (Table 1.1). The benefits of modern SFC have lead to the availability of a chromatographic tool that enables fast speeds and high resolution with low operating costs. SFC provides
performance now only beginning to be achieved through the use of UHPLC.
