An Overview of HPLC Methods for the Enantiomer Separation of Active Pharmaceutical Ingredients in Bulk and Drug Formulations

In recent years there has been considerable interest in the synthesis and separation of enantiomers of organic compounds especially because of their importance in the biochemistry and pharmaceutical industry. Major differences in biological activity have been observed in chiral molecules. These differences in stereochemistry can influence the pharmacological, metabolic or toxicological activity of the finished drug formulations. In other words isomer specific pharmaceuticals often exhibit increased potency, higher bioavailability and reduced side effects when compared to racemic pharmaceutical compounds. The development of new practical methods for the preparation of enantiomerically pure substances is thus vital and nowadays, pharmaceutical industry demands detailed investigations of chiral molecules, in compliance with the regulatory requirements. In this review some of the most important methods developed for the enantiomeric resolution by high pressure liquid chromatography, from the last decade, are described. The mechanisms of the different separation principles are briefly discussed. Also the major chiral stationary phases, commercially available, are presented, including a guide provided to help the readers selecting the appropriate chiral stationary phase. Finally the most common chiral selectors used as additives in mobile phases are described, including their advantages and their limitations.