Quantitation of the relative amounts of anhydrous carbamazepine (C15H12N2O) and carbamazepine dihydrate (C15H12N2O.2H2O) in a mixture by solid-state nuclear magnetic resonance (NMR).

Abstract

The application of solid state nuclear magnetic resonance (NMR) for the quantitation of the relative amounts of carbamazepine anhydrate (I) and carbamazepine dihydrate (II) in a mixture is presented. The techniques of cross polarization, dipolar decoupling, and magic angle spinning have been used to obtain high-resolution NMR spectra of the samples in the solid state. Although the chemical shifts of I and II were similar, the proton spin lattice relaxation time of II was much shorter than that of I. A delay time of 10 sec between pulses resulted in saturation of the signal from I and in a spectrum arising solely from II. The dependence of the observed signal intensity on the contact time was evaluated for II and glycine, the internal standard, to allow theoretical estimation of the peak area ratios. Various molar ratios of I and II were then mixed with glycine, and the resulting peak area ratios of II to the area of the alpha and the carbonyl carbons of glycine was linearly related to the relative proportion of II in the mixture.