Pure shift NMR experiments greatly enhance spectral resolution by collapsing peak multiplet structures into singlets. They have been demonstrated for a variety of samples over the past decade, such as natural products, beverages, and pharmaceutical ingredients. For aqueous samples, the intense water peak can cause added complications, such as overlap with signals of interest and dynamic range issues. When com bined with water suppression, pure shift NMR can be used for aqueous mixtures. Here, we demonstrate the combination of ultraclean pure shift NMR (i.e., SAPPHIRE) with two different water suppression schemes: one using WATERGATE (W5) pulses and another employing Excitation Sculpting (ES). Each method is demonstrated for the analysis of molecules of pharmaceutical interest in water and water/organic solvent mixtures. While SAPPHIRE-iW5 completely suppresses the water signal to the baseline level, its poor band-selectivity results in obliterating relevant resonances around the solvent frequency. SAPPHIRE-iES demonstrated superior results: it suppresses the water signal well, while retaining resonances very close to the solvent frequency. In addition, SAPPHIRE-iES allows flexibility in the settings of the selective pulse to handle variable water frequency typical for water/organic solvent mixtures.
