Chiral separations remain a decided area of interest, particularly in the pharmaceutical and agrochemical fields. Although high performance liquid chromatography (HPLC) remains a strong choice for separations because of its robustness, transferability, and instrument availability, the use of chiral supercritical fluid chromatography (SFC) continues to expand in analytical and preparative techniques. Several chiral stationary phases continue to enjoy wide use because of their broad application in both HPLC and SFC.
Chiral separations continue to be of great interest because of the prevalence of racemates in markets such as the pharmaceutical and agrochemical (pesticide) industries. In fact, a review of the importance of pharmaceutical chiral separations in single-enantiomer patent cases was recently published (1), and another review estimates that about 30% of pesticides are chiral with about half of these having multiple chiral features (2). The individual pesticide enantiomers may exhibit different effects on the environment. Although the separation of enantiomers can be challenging because of their identical physical and chemical properties in an achiral environment, chiral stationary phases (CSPs) have greatly facilitated enantioseparations in high performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC). Research on specialized separation techniques using novel CSPs, particularly derivatized polysaccharides and cyclodextrins, continues for the resolution of specific individual enantiomers, and chiral separation on commercially available CSPs remains a mature and widely used technique with some new entries to the market. Polysaccharide and macrocyclic glycopeptides CSPs continue to be the most widely used commercial chiral phases, with cyclodextrins, cyclofructans, π-complex, and protein-based CSPs also finding use. For non-HPLC separations such as gas chromatography (GC) and capillary electrophoresis (CE), cyclodextrins continue to dominate. Enantioseparations of larger, more-complex molecules with multiple chiral centers have increased as biotech continues to grow, meaning that more compounds must be resolved simultaneously, and chiral separations of more-polar molecules are needed, especially for the agrochemical and pharmaceutical fields.
There are plenty of resources and information available for performing chiral separations, both from the commercial suppliers of CSPs and in the literature. There are numerous reviews of the widely used CSPs, including recent reviews of cellulose and polysaccharide-based CSPs (3), protein and glycoprotein CSPs (4), macrocyclic antibiotic CSPs (5), cyclodextrin CSPs (6,7), and chiral ion- and ligand-exchange CSPs (8). Reflecting the burgeoning interest in SFC chiral separations of pharmaceuticals, several reviews specific to SFC have recently been published (9–12).The State of Current CSPs
Chiral separation continues to be the primary technique of choice, with many companies seeing an increase of about 20% for both analytical and preparative enantioseparations in their laboratories. The market continues to enjoy growth and maturation as older technologies are replaced by newer and improved technologies. New CSPs continue to be introduced to the market, including the zwitterionic phases, Chiralpak Zwix(+) and Zwix(-) from Chiral Technologies, a new immobilized crown-ether phase, Chiralpak CR-I also from Chiral Technologies, and an immobilized ovomucoid phase, C18-Ovo-5-120 from Separation Methods Technologies. Companies such as YMC America, Inc., Chiral Technologies, Diacel, and Separation Methods Technologies are continuing to expand their offerings of immobilized polysaccharide-derived CSPs because these columns offer greater stability, can be used with a wider variety of mobile phases, and are useful in both liquid chromatography (LC) and SFC applications.
One apparent trend in the market is toward the increased use of SFC for chiral separations. The advantages of SFC are the reduced environmental impact and operating costs with increased throughput. Although SFC has traditionally found more use in preparative-scale chiral separations, where the waste reduction and decreased solvent use is attractive to industry, these immobilized CSPs are also seeing increased use in analytical applications as well. SFC is currently receiving a lot attention from the pharmaceutical industry for screening and method development of chiral separations (13–15).