The effect of tube quality on externally calibrated quantitative nuclear magnetic resonance analysis: How bad can it be?

Externally calibrated quantitative nuclear magnetic resonance (NMR) approaches offer practical means to simultaneously evaluate chemical identity and content without the addition of calibrants to the test sample. Despite continuous advances in external calibration over the last few decades, adoption of these approaches has been slower than expected. Variations in NMR tube geometry are a commonly overlooked factor that can have a substantial effect on externally calibrated quantitation methods. In this report, we investigate the extent to which tube-to-tube volume variability can affect quantitative NMR outcomes. The results highlight the importance of considering tube quality during the development stages of externally calibrated quantitative methods. In addition, we propose a simple, yet effective volume correction strategy using the residual protonated solvent signal that, based on experiments with mixed NMR tubes of varying quality, alleviates the effect of tube-to-tube variability. Externally calibrated quantitative nuclear magnetic resonance (NMR) approaches offer practical means to evaluate chemical identity and content without the addition of calibrants to the sample. Despite continuous advances in external calibration, adoption of these approaches has been slower than expected. Variations in tube geometry are a commonly overlooked factor that can have a substantial effect on quantitation methods. In this report, we investigate the extent to which tube-to-tube variability can affect quantitative NMR outcomes. The results highlight the importance of considering tube quality during early method development stages. In addition, we propose a simple, yet effective volume correction strategy using the residual protonated solvent signal that alleviates the effect of tube-to-tube variability. image