Direct separation of nadolol enantiomers on a Pirkle-type chiral stationary phase

Abstract

The enantiomers of the β-adrenergic blocking drug nadolol may be separated on a chiral stationary phase following conversion to their 1-naphthylurea derivatives by reaction with the achiral reagent 1-naphthylisocyanate. A mixture of n-hexane, propan-2-ol and acetonitrile is used to elute the enantiomers from a column comprising ( R)-N-(3,5-dinitrobenzoyl)- l-leucine covalently bound to 5-μm aminopropylsilica. Nadolol is a cis-diol structure which has three stereogenic centres, however the two diol carbons are held in a fixed configuration and it therefore has only four optical isomers. These are resolved in under 30 mn using the procedure described herein, which is therefore suitable for use in the quality control context.