DETERMINATION OF THE OPTICAL PURITY AND ABSOLUTE-CONFIGURATION OF THREO-METHYLPHENIDATE BY PROTON NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY WITH CHIRAL SOLVATING AGENT

The direct determination of both the optical purity and absolute confi guration of threo-methylphenidate has been accomplished in a simple, s pecific, and accurate manner by H-1-NMR spectroscopy. The enantiomeric resonances of threo-methylphenidate were effectively resolved in CDCl 3 solution by the addition of the chiral solvating agents (R)-(-)-or ( S)-(+)-2,2,2,-trifluoro-1-(9-anthryl)ethanol. Optical purities were de termined on the basis of the intensities of the enantiomeric ester met hyl proton resonances; the assignment of enantiomeric configurations w as based on the relative field positions of these resonances and the e xamination of molecular models. The analysis of synthetic enantiomeric mixtures of threo-methylphenidate by the proposed NMR method resulted in assay values that agreed closely with the known quantities of each enantiomer in the mixtures tested. The mean +/-SD recovery value for the (2S,2'S)-(-)-threo-enantiomer, amounting to 99.9 +/- 0.6% of added (n = 10), correlated well with that previously found by H-1-NMR spect roscopy with a chiral Eu(III) shift reagent. However, the present appr oach is simpler, shows less reliance on reagents and solvents of a hig h purity, and does not require strict anaerobic working conditions.