LC-NMR for Natural Products Analysis: A Journey from an Academic Curiosity to a Robust Analytical Tool

Abstract

LC–NMR combines the advantage of the outstanding separation power of liquid chromatography (LC) and the superior structural elucidating capability of nuclear magnetic resonance (NMR). NMR has proved that it is a standout detector for LC by providing maximum structural information about plant originated extracts particularly in its isolating ability of isomeric (same molecular formula) and/or isobaric (same molecular weight) compounds as compared to other detectors. The present review provides an overview of the LC–NMR developmental trends and its application in natural products analysis. The different LC–NMR operational modes are described, as well as how technical improvements assist in establishing this powerful technique as an important analytical tool in the analysis of complex plant-derived compounds. On-flow, stop-flow and loop-storage modes, as well as the new offline mode LC–SPE–NMR and capLC-NMR configurations that avoid the ingestion of expensive deuterated solvents throughout the experiment are mentioned. Utilization of cryogenic probe and microprobe technologies which are the other important promising approaches for guaranteeing the sensitivity issues are also described. Concluding remarks and future outlooks are also discussed.

Metabolomics in the Context of Plant Natural Products Research: From Sample Preparation to Metabolite Analysis

“…Whereas standalone NMR spectroscopy has unquestionable merits, on-line hyphenation of separation techniques and NMR spectroscopy (HPLC-NMR) can provide another powerful workflow for de novo identification of novo natural products in crude extracts [154,155]. In hyphenated HPLC-NMR, a flow cell matching the HPLC module is used instead of conventional NMR probes [156]. The separated analytes are eluted from the HPLC column to the crossed flow cell, and their on-line-1 H NMR spectra are recorded.…”

Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives

“…Combining NMR with liquid chromatography (LC-NMR) and further with MS (LC-NMR-MS) through hardware hyphenation has been long done, especially in natural products analysis and the different ways of doing it have been nicely described recently ( Gebretsadik et al, 2019 ). This approach has also been found useful for drug metabolism ( Shockcor, 2002 ) and pharmaceutical research ( Lindon et al, 2000 ; Lindon et al, 2002 ).…”

Combined Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry Approaches for Metabolomics

“…However, this technique is limited by the time-evolving LC gradient composition which induces a bias in the NMR measurement. Indeed, this leads to an evolution of the position of the solvent peaks which makes it difficult to maintain an efficient solvent signal suppression over time . Most importantly, the short residence time of nuclear spins in the NMR detection cell strongly limits signal averaging, which in turns impacts the resulting NMR signal-to-noise ratio (SNR).…”

“…Schematic setups of the different LC-NMR working modes with parallel mass spectrometer (MS) detection: (a) online/continuous-flow mode, (b) stop-flow mode, and (c) loop/cartridge storage mode. Figure reproduced from ref under Creative Commons Attribution 4.0 International License ().…”