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 configuration of threo-methylphenidate has been accomplished in a simple, specific, and accurate manner by 1H-NMR spectroscopy. The enantiomeric resonances of threo-methylphenidate were effectively resolved in CDCl3 solution by the addition of the chiral solvating agents (R)-(-)- or (S)-(+)-2,2,2,-trifluoro-1-(9-anthryl)ethanol. Optical purities were determined on the basis of the intensities of the enantiomeric ester methyl proton resonances; the assignment of enantiomeric configurations was based on the relative field positions of these resonances and the examination 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 1H-NMR spectroscopy with a chiral Eu(III) shift reagent. However, the present approach is simpler, shows less reliance on reagents and solvents of a high purity, and does not require strict anaerobic working conditions.
Hanna
G M
GM
Food and Drug Administration, Department of Health and Human Services, New York Regional Laboratory, Brooklyn 11239-1593.
Lau-Cam
C A
CA
D009682:Magnetic Resonance Spectroscopy; D008774:Methylphenidate / Q000737:chemistry*; D008968:Molecular Conformation; D012997:Solvents; D013237:Stereoisomerism
D012997:Solvents; D008774:Methylphenidate