Optimization of enantiomeric separation for quantitative determination of the chiral drug propranolol by H-1-NMR spectroscopy utilizing a chiral solvating agent

High-field H-1-NMR methodology for enantiomeric composition determination o f the chiral drug propranolol utilizing a chiral solvating agent is reporte d, Optimal experimental conditions for the resolution of enantiomers were d etermined by studying the interaction of substrate concentration, chiral so lvating agent concentration and temperature. The success of the method is b ased on the selection of a chiral solvating agent that has the following tw o characteristics. First, it possesses functional groups that are complimen tary to those of the chiral substrate for significant interaction to occur. Second, it has a group of diamagnetic anisotropy near its stereogenic cent er for translating spatial environments of solute nuclei into different mag netic environments that are measurable by NMR spectroscopy. Optical puritie s were determined on the basis of the intensities of the methyl proton reso nances. The analysis of synthetic enantiomeric mixtures of propranolol by t he proposed NMR method resulted in assay values, which agreed closely with the known quantities of each enantiomer in the mixtures tested. The mean +/ - SD recovery values for the (R)-(+)-enantiomer was 100.0 +/- 0.6% of added antipode (n = 7). (C) 2000 Elsevier Science B.V. All rights reserved.