The accurate and efficient chiral separation of enantiomeric compounds is very important in fields such as pharmaceuticals, pesticides, and synthesis development. The striking differences in the chemical and physiological properties between enantiomers make these separations a key requirement in the development of many drugs. Often, only one enantiomer exhibits the desired therapeutic benefit, while the other may have an antagonistic effect—or even worse, a toxic side effect. A striking example of this behavior is the drug, thalidomide. Whereas R-thalidomide is an efficient sedative, S-thalidomide is a teratogen that caused severe birth defects in thousands of children in many countries. Since 1992, the US Food and Drug Administration (FDA) has required a complete, separate evaluation of the effects of all compounds that have the potential for chirality.

Chiral analysis separation is also very important when it comes to raw materials used during the development of chemical syntheses. In the field of peptide chemistry, amino acids are critical raw materials whose chiral purity must be assessed to develop reliable synthetic pathways to new compounds. In addition, it is highly desirable to evaluate potential enantiomeric excesses after each synthesis step is. And to ensure unwanted chiral conversions do not occur in the body, the final compound’s stability must be determined.

Chiral separations can be performed in several ways, including chiral derivatization and chromatographic techniques using either a chiral mobile phase additive or a chiral stationary phase. This summary discusses the benefits of chiral stationary phases and presents strategies for developing successful methods for chiral separations. Chiral Stationary Phases Chiral stationary phases have been in use since the early 1970s, when ligand exchange and protein-based phases were developed for high-performance liquid chromatography (HPLC).

Cyclodextrin-based and Pirkle-type phases were some of the first next-generation options to be introduced, and were soon followed by polysaccharide-based chiral stationary phases such as the Lux® portfolio of chiral LC/SFC columns. These phases were developed in the mid-1980s and greatly enhanced the capabilities of analytical and preparative chromatographic methods for chiral compounds (1). Macrocyclic glycopeptide-based and cinchona alkaloid-based phases were then developed in the early-to-mid 1990s.