Quantitative Nuclear Magnetic Resonance for Small Biological Molecules in Complex Mixtures: Practical Guidelines and Key Considerations for Non-Specialists

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical approach that enables both the structural determination and precise quantification of small molecules, such as metabolites. However, achieving precise quantification with NMR involves more than simply comparing integrals derived...

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Main Authors: Eva Drevet Mulard, Véronique Gilard, Stéphane Balayssac, Gilles J. P. Rautureau
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/8/1838
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author Eva Drevet Mulard
Véronique Gilard
Stéphane Balayssac
Gilles J. P. Rautureau
author_facet Eva Drevet Mulard
Véronique Gilard
Stéphane Balayssac
Gilles J. P. Rautureau
author_sort Eva Drevet Mulard
collection DOAJ
description Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical approach that enables both the structural determination and precise quantification of small molecules, such as metabolites. However, achieving precise quantification with NMR involves more than simply comparing integrals derived from NMR peaks to a concentration reference; quantitative NMR (qNMR) is a distinct and specialized application within the field. To obtain absolute quantitative results, spectra must be acquired under strict experimental conditions. Unfortunately, these acquisition parameters can be challenging to implement experimentally and often require trade-offs that compromise high throughput or practicality. In such situations, alternative strategies based on relative quantification and advanced software tools offer valuable solutions. This review aims to provide non-specialists with the key concepts and methodologies required for accurate NMR-based quantification in biomedical research, focusing on practical guidelines and experimental considerations. Unlike prior reviews, it prioritizes accessibility and practical implementation for researchers outside the field, emphasizing key experimental workflows and applications in biological and clinical studies. It clarifies the distinctions between absolute and relative concentration determinations and emphasizes the critical importance of sample preparation, pulse sequence selection, and rigorous control of experimental parameters. Recent technological advancements, such as high-field spectrometers and cryoprobes, have significantly enhanced the sensitivity and accuracy of NMR, enabling the reliable detection of low-concentration metabolites. Quantitative NMR thus offers critical potential in elucidating metabolic processes, supporting drug development, and aiding disease diagnosis.
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spelling doaj-art-ffb4c3b9fa474378be1ea75943f52ce62025-08-20T02:18:15ZengMDPI AGMolecules1420-30492025-04-01308183810.3390/molecules30081838Quantitative Nuclear Magnetic Resonance for Small Biological Molecules in Complex Mixtures: Practical Guidelines and Key Considerations for Non-SpecialistsEva Drevet Mulard0Véronique Gilard1Stéphane Balayssac2Gilles J. P. Rautureau3Institute of Chemistry and Biochemistry (ICBMS), UMR 5246, CNRS, University Lyon, F-69622 Villeurbanne, FranceLaboratoire Softmat, CNRS UMR 5623, Université de Toulouse, F-31062 Toulouse, FranceLaboratoire Softmat, CNRS UMR 5623, Université de Toulouse, F-31062 Toulouse, FranceInstitute of Chemistry and Biochemistry (ICBMS), UMR 5246, CNRS, University Lyon, F-69622 Villeurbanne, FranceNuclear magnetic resonance (NMR) spectroscopy is a powerful analytical approach that enables both the structural determination and precise quantification of small molecules, such as metabolites. However, achieving precise quantification with NMR involves more than simply comparing integrals derived from NMR peaks to a concentration reference; quantitative NMR (qNMR) is a distinct and specialized application within the field. To obtain absolute quantitative results, spectra must be acquired under strict experimental conditions. Unfortunately, these acquisition parameters can be challenging to implement experimentally and often require trade-offs that compromise high throughput or practicality. In such situations, alternative strategies based on relative quantification and advanced software tools offer valuable solutions. This review aims to provide non-specialists with the key concepts and methodologies required for accurate NMR-based quantification in biomedical research, focusing on practical guidelines and experimental considerations. Unlike prior reviews, it prioritizes accessibility and practical implementation for researchers outside the field, emphasizing key experimental workflows and applications in biological and clinical studies. It clarifies the distinctions between absolute and relative concentration determinations and emphasizes the critical importance of sample preparation, pulse sequence selection, and rigorous control of experimental parameters. Recent technological advancements, such as high-field spectrometers and cryoprobes, have significantly enhanced the sensitivity and accuracy of NMR, enabling the reliable detection of low-concentration metabolites. Quantitative NMR thus offers critical potential in elucidating metabolic processes, supporting drug development, and aiding disease diagnosis.https://www.mdpi.com/1420-3049/30/8/1838quantitative NMRmetabolomicsbiochemistrybiomoleculesmetabolites
spellingShingle Eva Drevet Mulard
Véronique Gilard
Stéphane Balayssac
Gilles J. P. Rautureau
Quantitative Nuclear Magnetic Resonance for Small Biological Molecules in Complex Mixtures: Practical Guidelines and Key Considerations for Non-Specialists
Molecules
quantitative NMR
metabolomics
biochemistry
biomolecules
metabolites
title Quantitative Nuclear Magnetic Resonance for Small Biological Molecules in Complex Mixtures: Practical Guidelines and Key Considerations for Non-Specialists
title_full Quantitative Nuclear Magnetic Resonance for Small Biological Molecules in Complex Mixtures: Practical Guidelines and Key Considerations for Non-Specialists
title_fullStr Quantitative Nuclear Magnetic Resonance for Small Biological Molecules in Complex Mixtures: Practical Guidelines and Key Considerations for Non-Specialists
title_full_unstemmed Quantitative Nuclear Magnetic Resonance for Small Biological Molecules in Complex Mixtures: Practical Guidelines and Key Considerations for Non-Specialists
title_short Quantitative Nuclear Magnetic Resonance for Small Biological Molecules in Complex Mixtures: Practical Guidelines and Key Considerations for Non-Specialists
title_sort quantitative nuclear magnetic resonance for small biological molecules in complex mixtures practical guidelines and key considerations for non specialists
topic quantitative NMR
metabolomics
biochemistry
biomolecules
metabolites
url https://www.mdpi.com/1420-3049/30/8/1838
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