The Chromatography Forum

of Delaware Valley

Over the past 25 years, there have been some major breakthroughs in the field of chiral chromatography. Prior to 2002, most chiral HPLC separations were done by normal phase chromatography using an alkane (heptane or hexane), and an alcohol (ethanol or IPA). The success rate was only about 60% and there was only a handful of chiral columns available at the time which included AD, OD, OJ, and AS. However, in 2002, Chiral Technologies discovered that these coated chiral stationary phases were more stable than originally thought. The “polar organic” mobile phase was introduced. Acetonitrile, methanol, and IPA were used in the mobile phase to replace normal phase chromatography. This was particularly useful in terms of solubility and also helped resolve moderate to tenacious binders which did not elute by either SFC or by normal phase HPLC conditions. In 2004, the second major breakthrough occurred. Chiral Technologies introduced the first immobilized chiral stationary phase, IA. Immobilized chiral stationary phases are unique in that they are not coated to the silica gel but are rather covalently bound to the silica gel support. The result is a more stable and more rugged chiral column. These immobilized chiral stationary phases are essentially indestructable and are stable to a wide range of solvents including DCM, TBME, ethyl acetate, and THF. This advancement has enabled the discovery of very unique chiral separations which may have encountered solubility issues. The final major breakthrough which occurred in the past 25 years is chiral separations with supercritical fluid chromatography, or SFC. In SFC, the weak component of the mobile phase has been replaced by CO2. This allows for much “greener” separations of weak to moderate binders. This talk will outline practical examples of each of these advancements.