Determination of the enantiomeric composition of cycloprofen by proton nuclear magnetic resonance spectroscopy with a europium(III) shift reagent

Abstract

The enantiomeric composition of cycloprofen was determined in a simple and reliable manner by proton nuclear magnetic resonance spectroscopy with a chiral Europium(III) shift reagent. Effective complexation with the shift reagent took place in CCl₄ after conversion of the enantiomeric sample into a mixture of the methyl ester derivatives. Optimisation of the experimental conditions in terms of substrate concentration and shift reagent to substrate molar ratio led to two sets of enantiomeric resonance signals of utility for quantitative purposes. Analysis of synthetic enantiomeric mixtures by the proposed method demonstrated an excellent agreement between the assay results and the known masses of each enantiomer present in the mixture samples. The average ± standard deviation recovery values were 100.1 ± 0.4%(n= 6) and 99.9 ± 0.6%(n= 6) of (–)-cycloprofen depending on whether the quantification is based on the α-methyl protons or ester methyl protons, respectively.