Recent progress in chiral stationary phase development and current chiral applications

Oct 01, 2012

Chiral separations remain a decided area of interest, as well as an all-too-often puzzle and on-going problem for many industries. High performance liquid chromatography (HPLC) remains the method of choice for most separations because of its robustness, transferability and instrument availability. Several chiral stationary phases continue to enjoy wide use in part because of their broad application. More recently, developed phases such as cyclofructans are finding increased use in HPLC and separation techniques. This brief review is an update on some of the latest chiral offerings.

Chiral separations in high performance liquid chromatography (HPLC) continue to be of great interest because of their prevalence in diverse areas such as the pharmaceutical industry, agrochemicals and food additives. Separation of enantiomers can be challenging because of their identical physical and chemical properties in an achiral environment. The advent of chiral stationary phases (CSPs) has been a boon to the field of enantioseparations. While research on specialized separation techniques using novel CSPs continues for the resolution of specific individual enantiomers, chiral separations on commercially available CSPs are a mature and widely used technique. Polysaccharide and macrocyclic glycopeptide CSPs remain the most widely used commercial chiral phases, with cyclodextrin-, cyclofructan-, π-complex- and protein-based CSPs also finding use. For non-HPLC separations, such as gas chromatography (GC) and capillary electrophoresis (CE), cyclodextrins dominate. The HPLC enantioseparation of larger molecules and multiple chiral centres has increased as the influence of biotech grows, and more polar molecules are of interest in discovery laboratories. Recently, the most important and widely used CSPs for HPLC were reviewed with sections on enantiorecognition mechanisms (1). There are plenty of resources and information available for one needing to perform chiral separations. Reviews have recently been published on general chiral HPLC methods for pharmaceutical analysis (2–4) and for supercritical fluid chromatography (SFC) separations of pharmaceuticals (5,6), including preparative-scale separations.

The State of Current CSPs

Chiral separation by HPLC continues to be the primary technique of choice, with many companies seeing an increase in the number of enantioseparations in their laboratories. The market continues to enjoy growth and maturation as older technologies are replaced by newer and improved technologies. A case in point is the expiration of the patent for the traditional coated Daicel columns (Daicel Corporation). Coated-type amylose and cellulose derivative CSPs are now offered by many companies and they remain one of the most important commercial CSPs. Daicel has started offering new bonded polysaccharide CSPs, which are advantageous for reversed-phase modes, mass spectrometry (MS) detection and preparative separations. A new class of commercial CSPs comprises the cyclofructan phases invented by Professor Daniel W. Armstrong (available through AZYP and Supelco/Sigma-Aldrich as the LARIHC and FRULIC columns). These phases are useful for the enantioseparation of primary amines.

Two apparent trends in the market are the increased use of SFC and smaller particles. The advantages of each are the reduced environmental impact and operating costs, as well as increased throughput. However, particles with diameters less than 3 μm are not commercially available, limiting microscale techniques. SFC has found more use particularly in preparative scale chiral separations, where the waste reduction and decreased solvent use is attractive to industry.