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

Abstract 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 ( 1 H‐ 1 H 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.