A Strategy for Developing HPLC Methods for Chiral Drugs

Molecules that relate to each other where an object and its mirror image are not superimposable are called chiral (from Greek word cheiro, meaning “hand”); that is, they are like a pair of hands. These molecules also are called enantiomers. Major differences in biological activity have been observed in chiral molecules. The difference in spatial arrangements of atoms in a molecule (that is, its stereochemistry) can influence its pharmacological, metabolic, or toxicologic activity. This is why regulatory requirements in the pharmaceutical industry demand detailed investigations of chiral molecules. Before initiating method development, it is important to develop a basic understanding of stereochemistry (1–5). Basic information on stereochemistry is provided in this article to help readers develop better understanding of the separation mechanisms that come into play in various separation methods used for chiral compounds. This knowledge can allow readers to select a desirable chiral separation method, based upon the molecular structure of the chiral compound of interest. Logical reasons for the selection process are discussed later in this article.