Liquid and high-pressure carbon dioxide chromatography of β-blockers : Resolution of the enantiomers of nadolol

Abstract

The enantiomers of six chiral aryloxypropanolamine β-blockers were separated by high-performance liquid chromatography on a column of modified cellulose immobilized onto silica (Chiralcel OD), using mixtures of heptane or hexane with a polar modifier. The quality of the separations was improved and retention times were reduced by eluting under subcritical conditions with carbon dioxide containing 20% of methanol. Nadolol, which has two chiral centres, gave three peaks instead of four on Chiralcel OD. A separation of the four isomers was obtained on α 1-acid glycoprotein column eluted with an aqueous buffer containing octanoate ions. A direct separation of the two diasteromers could not be obtained with achiral stationary phases, but the derivative formed by the base-catalysed reaction of nadolol with isopropyl isocyanate was well resolved on a column of amino-bonded silica eluted with carbon dioxide—methanol. This paper demonstrates the advantages of high-pressurecarbon dioxide chromatography for the analysis of stereoisomers.