Enhancing Sensitivity\nin the Hyphenation of High-Performance\nLiquid Chromatography to Benchtop Nuclear Magnetic Resonance Spectroscopy\nat Isocratic and Onflow Conditions

The onflow hyphenation of high-performance liquid chromatography\n(HPLC) in adsorption mode with a benchtop <sup>1</sup>H nuclear magnetic\nresonance (NMR) spectrometer is described for the first time. Protonated\nsolvents and isocratic conditions are used. The sensitivity was increased\nby choosing suitable NMR acquisition parameter as well as optimizing\ninjection parameters and postacquisition data processing methods.\nWith optimized conditions, the limit of detection (LOD) and the limit\nof quantification (LOQ) were LOD = 0.010 g L<sup>–1</sup> and\nLOQ = 0.031 g L<sup>–1</sup> for the methoxy <sup>1</sup>H\nof methyl paraben at 4.07 ppm, LOD = 0.038 g L<sup>–1</sup> and LOQ = 0.134 g L<sup>–1</sup> for the aromatic <sup>1</sup>H of pentyl paraben between 7.00 and 8.50 ppm. These are expressed\nin injection concentration and are comparable to existing HPLC hyphenation\nwith high-field NMR spectrometers. The analysis of a 2 g L<sup>–1</sup> paraben mixture, far below the legal limits for usage in cosmetics,\nillustrates the applicability of the method. Taking advantage of the\nspectral resolution, chromatographically overlapping peaks are resolved\nusing analyte-specific NMR elution traces. A methodology is detailed\nto facilitate the transfer of the optimized method to other (analyte)\nsystems.