Solvent suppression in pure shift NMR

Abstract

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 perdeuteriated form, for example when analysing 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, ultra-high 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 an eye-drop formulation of atropine.

Ultra-clean pure shift NMR with optimal water suppression for analysis of aqueous pharmaceutical samples

“…We thank Emma Gates, Dr Jonathan Bradley, Dr Daniel Berry, Prof. Mathias Nilsson, Prof. Gareth A. Morris, Dr Ralph W. Adams, and Dr Laura Castañar for sharing a preprint (https://doi.org/10.26434/chemrxiv-2023-kk2hn) 21 describing related work, carried out independently.…”