Solvent Suppression in Pure Shift NMR

• Published in: Analytical chemistry (Washington) 2024-03, Vol.96 (9), p.3879-3885
• Main Authors: Gates, Emma L., Bradley, Jonathan P., Berry, Daniel B. G., Nilsson, Mathias, Morris, Gareth A., Adams, Ralph W., Castañar, Laura
• Format: Article
• Language: English
• Subjects: Atropine; Cyanocobalamin; Dietary supplements; Formulations; NMR; Nuclear magnetic resonance; Protons; Solvents; Spectra; Vitamin B12
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.3c05379

Intense solvent signals in 1H solution-state NMR experiments typically cause severe distortion of spectra and mask nearby solute signals. It is often infeasible or undesirable to replace a solvent with its perdeuterated form, for example, when analyzing formulations in situ, when exchangeable protons are present, or for practical reasons. Solvent signal suppression techniques are therefore required. WATERGATE methods are well-known to provide good solvent suppression while enabling retention of signals undergoing chemical exchange with the solvent signal. Spectra of mixtures, such as pharmaceutical formulations, are often complicated by signal overlap, high dynamic range, the narrow spectral width of 1H NMR, and signal multiplicity. Here, we show that by combining WATERGATE solvent suppression with pure shift NMR, ultrahigh-resolution 1H NMR spectra can be acquired while suppressing intense solvent signals and retaining exchangeable 1H signals. The new method is demonstrated in the analysis of cyanocobalamin, a vitamin B12 supplement, and of an eye-drop formulation of atropine.