Direct enantiomeric purity determination of the chiral anesthetic drug bupivacaine by H-1 NMR spectroscopy

The direct determination of the enantiomeric purity of the chiral anaesthet ic drug bupivacaine has been developed using H-1 NMR (400 MHz) spectroscopy with a chiral solvating agent. Optimization of experimental conditions in terms of temperature, substrate concentration and solvating agent to substr ate molar ratio provided two significant signal splittings for chiral recog nition resulting from diastereomeric solvation. Based on the relative inten sities of the aliphatic methyl resonances assigned to (S)-(-)- and (R)-(+)- bupivacaine, the analysis of synthetic mixtures of the enantiomers by the p roposed NMR method resulted in assay values which agreed closely with the k nown quantities of each enantiomer in the mixtures tested. The mean PSD rec overy values for the (R)-(+)-enantiomer was 100.0 +/- 0.6% of added antipod e (n = 7). The optically pure enantiomers were used to establish the minimu m sensitivity of the NMR spectroscopic method of chiral analysis.