DETERMINATION OF EPHEDRINE, PSEUDOEPHEDRINE, AND NOREPHEDRINE IN MIXTURES (BULK AND DOSAGE FORMS) BY PROTON NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

A simple, specific, and accurate H-1 nuclear magnetic resonance (NMR) spectroscopic method has been developed for quantitative determination of the Ephedra alkaloids (-)-ephedrine, (+)-pseudoephedrine, and (+/- )-norephedrine, either singly or in mixtures with each other, Determin ation of individual alkaloids was carried out in D2O solution, with ac etamide as internal standard. Although calculations were based on inte grals for the C-CH3 protons, those for the N-CH3 and -CH-O- protons ma y also be useful, depending on the compound, Determination of diastere omeric cross-contamination of ephedrine and pseudoephedrine-or of the concentrations of these alkaloids in the presence or absence of (+/-)- norephedrine-was feasible by using the integrals for the -CH-O- proton s after addition of a trace of DCI., Mean recoveries for ephedrine and pseudoephedrine from their respective synthetic mixtures with the int ernal standard (acet- amide) were greater than or equal to 99.9 +/- 0. 6% (n = 10) and 99.6 +/- 0.8% (n = 10) of the amount added. Recovery f or pseudoephedrine from diastereomeric mixtures with ephedrine was >99 .4 +/- 0.7% (n = 10) of the amount added, with as little as 1.92% stil l being measurable, Mean recovery of (+/-)-norephedrine from mixtures with ephedrine and pseudoephedrine was >99.7 +/- 2.5% (n = 4) of the a mount added, with about 1% still being measurable. Application of the proposed NMR spectroscopic method to commercial dosage forms, includin g ephedrine sulfate injections and pseudoephedrine hydrochloride table ts, yielded assay results ranging from 97.8 to 100.2% (mean, 99.2%) an d from 98.7 to 100.5% (mean, 99.7%) of declared, respectively.