Online Coupling of 80 MHz Benchtop 2D‐COSY NMR to HPLC

HPLC is coupled online for the first time to 2D-NMR on a benchtop NMR spectrometer. The potential is demonstrated at 80 MHz with COSY (1H-1H COrrelation SpectroscopY) for a mixture of methyl and propyl parabens, additives commonly used in cosmetics. To lessen the impact of short residence time in the NMR flow cell, a repetition delay reduction combined with non-uniform sampling (NUS) allows decreasing the COSY experiment duration from 1 h to 2 min. The HPLC-benchtop 2D-NMR online coupling is established for the first time, using three different modes: stop-flow (with short stops at the analyte peaks and in the baseline), slow-flow (with a lower, constant flow rate over the whole elution range of analytes) and steady-flow (with a constant flow rate throughout the experiment). The HPLC-benchtop 2D-NMR online coupling allows the successful separation and characterization of methyl and propyl parabens at low field. This provides more in-depth chemical information on separated analytes than HPLC-benchtop 1D-NMR, with a smaller footprint, reduced experimental complexity and at lower costs than HPLC-high-field 2D-NMR. It opens the way to other 2D-NMR experiments and the characterization of a wider range of analytes such as oligomers, small molar mass additives, or polymers.