In NMR spectroscopy, samples are usually dissolved in deuterated solvents to avoid overlap of small analyte signals with large, protonated solvent signals. However, for reasons such as cost and widespread use, using deuterated solvents is impractical, e.g., for on-flow NMR applications, since large volumes of solvent are required. This study compares six different solvent suppression techniques: PRESATuration (PRESAT), Water suppression Enhanced through T1 effects (WET), Pulsed Gradient STimulated Echo (PGSTE), 1-pulse-spoil, simple solvent subtraction, and a newly developed post-acquisition suppression method named Solvent Attenuation by Fourier Elimination (SAFE). The SAFE method is based on alternating measurements of the sample solution and the pure solvent 2n times, followed by a fast Fourier transform to eliminate the solvent signals, which are constant in the first approximation. The different solvent suppression methods were compared alone and in several combinations to determine their optimum suppression efficiency. The suppression was quantified by evaluating the Analyte-to-Solvent Ratio normalized to the unsuppressed 1H reference spectrum (ASRnorm). Furthermore, a comparison was made between the methods concerning their suitability for polymer solutions of varying molar masses, quantification towards measurement time efficiency, repeatability, and intermediate precision. The PGSTE-SAFE combination proved to be the most efficient method for polymer samples, achieving an ASRnorm of about 47,000. The applicability of solvent suppression methods in flow-based setups was also assessed by investigating polystyrenes in non-deuterated solvents. WET, PGSTE, and a WET-PGSTE combination were applied in online Size Exclusion Chromatography-NMR (SEC
NMR) to demonstrate their potential for efficient solvent suppression in this context.
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