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Optical Purity Determination of threo-Methylphenidate Hydrochloride Using a Chiral Europium Nuclear Magnetic Resonance (NMR) Shift Reagent

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Abstract

A 1H-NMR spectroscopic method for the determination of the optical purity of threo-methylphenidate hydrochloride is presented. Complexation of the free-base form of the substrate with a chiral Eu(III) shift reagent resulted in two distinct enantiomeric ester methyl proton signals of utility for quantitative work. The accuracy of the method was validated by analyzing six synthetic mixtures of various proportions of ( + )- and (–)-threo-methylphenidate. In addition to yielding assay results that were in close agreement with the known weights of each enantiomer in the mixture, and a mean recovery of the (–)-threo-enantiomer of better than 99.0%, the proposed method was capable of accurately measuring as little as 2% of one enantiomer in the presence of the other.

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Authors and Affiliations

  1. Food and Drug Administration, Department of Health and Human Services, New York Regional Laboratory, 850 Third Avenue, Brooklyn, New York, 11232-1593

    George M. Hanna

  2. Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, New York, 11439

    Cesar A. Lau-Cam

Authors
  1. George M. Hanna
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  2. Cesar A. Lau-Cam
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Hanna, G.M., Lau-Cam, C.A. Optical Purity Determination of threo-Methylphenidate Hydrochloride Using a Chiral Europium Nuclear Magnetic Resonance (NMR) Shift Reagent. Pharm Res 7, 726–729 (1990). https://doi.org/10.1023/A:1015815605583

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