Assessing the Detection Limit of a Minority Solid-State Form of a Pharmaceutical by 1 H Double-Quantum Magic-Angle Spinning Nuclear Magnetic Resonance Spectroscopy.

The lower detection limit for 2 distinct crystalline phases by ¹ H magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) is investigated for a minority amount of cimetidine (anhydrous polymorph A) in a physical mixture with the anhydrous HCl salt of cimetidine. Specifically, 2-dimensional ¹ H double-quantum (DQ) MAS NMR spectra of polymorph A and the anhydrous HCl salt constitute fingerprints for the presence of each of these solid forms. For solid-state NMR data recorded at a ¹ H Larmor frequency of 850 MHz and a MAS frequency of 30 kHz on ∼10 mg of sample, it is shown that, by following the pair of cross-peaks at a ¹ H DQ frequency of 7.4 + 11.6 = 19.0 ppm that are unique to polymorph A, the level of detection for polymorph A in a physical mixture with the anhydrous HCl salt is a concentration of 1% w/w.
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