What is the potential of measuring the enantiomeric ratio of drugs using supercritical fluid chromatography–MS?

Analytical chemists are always looking for more efficient techniques to meet analytical challenges of today’s regulatory and scientific requirements. One technique that has made drastic improvements in recent years is supercritical fluid chromatography (SFC). Since its early days, this separation technique has emerged as a powerful tool for both analytical and preparative scientists. In 2012, new instruments for analytical purpose were introduced that offer reliability, robustness and sensitivity never before possible. Since then, the interest in this technique was renewed. Indicated by the number of peerreviewed articles, analytical SFC progressively increased within the last 25 years. The use of supercritical fluids (sc) as mobile phases in chromatography presents unique advantages compared with traditional HPLC: low viscosity and high diffusivity allow faster and more efficient separations than HPLC. Coupling SFC to MS instruments is straightforward as carbon dioxide is easily eliminated during desolvation and provides low LODs and LOQs as well as additional structural information [1]. A wide range of analytes may be covered by SFC, including nonpolar, polar and charged compounds [2]. Applications for a broad variety of polarity are reported ranging from hydrocarbons, esters, amines, aldehydes, alcohols, carboxylic acids, amides, amphoterics, complexes to peptides. In general, supercritical carbon dioxide (CO 2,sc ) is used as mobile phase due to its easy generation and low toxicity. The more polar analytes can be separated by addition of modifiers and additives (mainly methanol and also even water). Thus, SFC is emerging as a technique of choice for enantioselective separations and as replacement for HPLC methods [3]. A positive side effect is the reduction of toxic solvents compared with HPLC, which can minimize waste and decrease the cost of chiral separations significantly.