A New Approach for the Direct Resolution of Racemic Beta Adrenergic Blocking Agents by HPLC

Abstract

Although beta-adrenergic blocking agents are a relatively new group of drugs, they have proven to be very useful in medical pharmacology. Since the successful introduction of propranolol (Inderal) a variety of analogous compounds have been developed. Most beta-blockers are racemic modifications and it is known that their enantiomers have different potencies and pharmacological effects. Hence, there has been considerable impetus for the production and study of the pure enantiomers. The chromatographic separation of these compounds has been dominated by the protein-based chiral stationary phases. Although selective, protein columns have limited capacity and stability. An efficient, alternative method has been found that does not suffer from the limitations of the protein phases. By using an unusual mobile phase consisting of a mixture of polar organic solvents in conjunction with the original native cyclodextrin bonded phase, the following compounds were resolved: propranolol, metoprolol, timolol, atenolol, cateolol alprenolol, pindolol, oxprenolol, labetolol and nadolol. These cyclodextrin chiral stationary phases have exceptional stability when used with these mobile phases. In addition, these separations are easily scaled to preparative proportions.