Determination of diastereomeric purity of tranylcypromine sulfate by proton magnetic resonance spectroscopy with lanthanide shift reagent

Use of proton nuclear magnetic resonance spectroscopy and the lanthanide shift reagent, Eu(hfc)3, resulted in a simple and reliable method for determination of the diastereomeric purity of trans-2-phenylcyclopropylamine sulfate (tranylcypromine sulfate). Eu(hfc)3 effectively simplified the complex overlapping pattern of the 5 non-equivalent phenyl protons to a virtually first order pattern. At a shift reagent to substrate molar ratio of 0.75, and a substrate concentration of 0.25M (as the free base) in CDCl3, the resonances for the cis- and trans-ortho-phenyl protons at 11.39 and 9.99 ppm, respectively, were sufficiently resolved to be of use in quantitative work. Analysis of synthetic diastereomeric mixtures of 2-phenylcyclopropylamine sulfate by the proposed method yielded results that were in close agreement with the expected values. The mean recovery (SD) of trans-diastereomer was 100.51% (0.40) (n = 6). Levels of less than 2% of cis-diastereomer were measurable in cis-trans mixtures.