One sample, two stories: A comparative dive into NMR and LC-HRMS metabolomics in natural products and foods

Metabolomics has emerged as a powerful approach for characterizing the chemical complexity of natural products and foods, enabling the discovery of bioactive compounds, assessment of nutritional quality, and authentication of sources. Among the arsenal of analytical tools available, NMR spectroscopy and LC-HRMS are widely regarded for their complementary strengths. This study presents a comparative investigation of these two platforms using identical samples derived from diverse natural matrices, i.e. leaves from Pistacia lentiscus var. Chia , honey and table olives, showcasing how each technique offers a distinct narrative of the metabolome. NMR spectroscopy excels in delivering highly reproducible, quantitative data with minimal sample preparation and provides direct structural information. In contrast, LC-HRMS boasts superior sensitivity, allowing the detection of a vast array of low-abundance and chemically diverse metabolites, albeit often with challenges in quantitative information and structural confirmation. By applying both methods to the same set of samples, key differences in metabolite coverage, compound annotation rates, and data complexity were highlighted in the different matrices [ 1 ] [ 2 ] [ 3 ]. Through non-targeted metabolite profiling and multivariate analysis, we demonstrated how NMR and LC-HRMS each uncover unique aspects of the metabolic landscape. This dual-platform approach underscores the importance of methodological complementarity in metabolomics, ultimately enhancing the metabolite annotation confidence. Through this “one sample, two stories” paradigm, we propose integrative workflows that exploit the strengths of both NMR and LC-HRMS to unravel the full complexity of metabolomes in natural and food products. Acknowledgments This work was supported by the “GreenCosmIn” project (HORIZON-MSCA-2022-SE-01, project code: 101131346). Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany