Application of Standard HSQC‐ME Pulse Sequence on Benchtop NMR Devices for Quantitative Applications

The heteronuclear single quantum correlation (HSQC) NMR method is widely used for the structural characterization of complex mixtures. In this study, the application range of multiplicity‐enhanced HSQC (HSQC‐ME) spectroscopy was broadened to quantitative analysis on low‐field NMR devices with standard measurement possibilities. Acquisition parameters such as number of scans and t1 increments as well as repetition time were optimized to achieve the best signal‐to‐ratio and resolution requiring minimum measurement time. Standardization with internal standard using correction factor and external calibration approaches for active pharmaceutical ingredients/stimulants in pharmaceutical products and dietary supplements showed average absolute bias of 5.0% and 7.7%, respectively. The HSQC‐ME NMR spectroscopic method was characterized by measurement uncertainty below 4% and limits of detection below 3 mg/mL for 2‐h measurement time. Semiquantitative HSQC‐ME analysis of organic acids in e‐cigarettes can be performed within the accuracy of 25% at low‐field NMR instruments in case of overlap in 1D NMR dimension and in the presence of huge solvent signals.