Chiral Differences in the Disposition of the Quaternary Anticholinergic Drug Oxyphenonium Bromide

Abstract

As for many other anticholinergic drugs, the enantiomers of oxyphenonium bromide exhibit large differences in affinity to muscarinic receptors as well as in therapeutic effect [1]. For detailed study of the fate of the enantiomers in the body an assay is required that determines both enantiomers simultaneously in the biological sample. Although various chiral Chromatographic systems have been developed over the years [2], we were unable to separate the enantiomers of oxyphenonium bromide [3]. Recently we succeeded in resolving racemic oxyphenonium bromide on an α₁-acid glycoprotein (EnantioPac®) column; but this system had insufficient efficiency and stability for bioanalytical applications. In order to study differences between oxyphenonium bromide enantiomers in absorption, distribution, metabolism and excretion, another approach was adopted, in which the enantiomers were synthesized separately (Fig. 1).