Chiral Purity

Chiral purity assessment quantifies the enantiomeric composition of a compound bearing one or more stereocentres, expressed as enantiomeric excess (the...

Chiral purity assessment quantifies the enantiomeric composition of a compound bearing one or more stereocentres, expressed as enantiomeric excess (the difference between the proportions of the two enantiomers present) or, increasingly, as the direct percentage of each individual enantiomer. Chiral purity assessment is of particular pharmaceutical importance because the two enantiomers of a chiral drug frequently display markedly different pharmacological activity, potency, or toxicity — the thalidomide tragedy remaining the most widely cited historical illustration of this principle — such that regulatory authorities require chiral purity to be established and controlled for any enantiomerically defined drug substance. Chiral HPLC, employing a chiral stationary phase (commonly based on modified cellulose or amylose derivatives) capable of differentially retaining the two enantiomers through diastereomeric-like interaction, is the most widely used analytical technique for chiral purity determination, complemented in specific cases by chiral capillary electrophoresis or polarimetry.