1H-NMR studies of drugs with chiral solvating agent: the direct enantiomeric purity determination of the chiral anesthetic, prilocaine.

Abstract

Chiral recognition of prilocaine was obtained on a 400 MHz 1H-NMR spectrometer by fast diastereomeric interactions with the chiral solvating agent (S)-(+)-2,2,2-trifluoro-1-(9-anthryl) ethanol (TFAE). Assignment of absolute configuration was based on relative field position of the resolved enantiomeric signals. Influence of temperature, substrate concentration and solvating agent to substrate molar ratio on enantiomeric resolution were studied and evaluated. Optimization of experimental conditions provided two significant resolved signals for quantitative use. Utilizing the relative intensities of the resolved enantiomeric signals of the methine proton attached to the stereogenic center assigned to (S)-(+)- and (R)-(-)-prilocaine, the analysis of synthetic mixtures of the enantiomers by the proposed NMR method resulted in assay values which agreed closely with the known quantities of each enantiomer in the tested mixtures. The mean +/- SD recovery values for the (S)-(+)-enantiomer was 99.9 +/- 0.2% of added antipode (n = 7). The optically pure enantiomers were used to establish the minimum amount detected by the proposed NMR spectroscopic method.