Hyperpolarized nuclear magnetic resonance (NMR) offers an ensemble of methods that remarkably address the sensitivity issues of conventional NMR. Dissolution Dynamic Nuclear Polarization (d-DNP) provides a unique and general way to detect 13 C NMR signals with a sensitivity enhanced by several orders of magnitude. The expanding application scope of d-DNP now encompasses the analysis of complex mixtures at natural 13 C abundance. However, the application of d-DNP in this area has been limited to metabolite extracts. Here, we report the first d-DNP-enhanced 13 C NMR analysis of a biofluid -urine-at natural abundance, offering unprecedented resolution and sensitivity for this challenging type of sample. We also show that accurate quantitative information on multiple targeted metabolites can be retrieved through a standard addition procedure.
Metabolomics provides crucial information on the metabolism of living organisms, by detecting and quantifying metabolites in biofluids, biopsies or extracts. Metabolomics studies involve analysing large collections of very complex samples by NMR or mass spectrometry methods. The resulting 1D spectra are characterized by the ubiquitous overlap between metabolite signals, justifying the need for the acquisition of 2D spectra on such samples. However, the long acquisition time of conventional 2D NMR makes it incompatible with the high-throughput nature of metabolomics, which explains why the acquisition of 2D spectra is generally limited to a subset of samples. In this chapter, we will describe how fast 2D NMR methods can lead to experimental times that become compatible with the systematic incorporation of 2D NMR in metabolomics workflows. The most frequently used 2D NMR methods include non-uniform sampling and ultrafast 2D NMR, but fast-pulsing methods and Hadamard spectroscopy have also shown some potential. In this chapter, we highlight how fast 2D NMR can facilitate the identification of biomarkers in untargeted metabolomics studies. We also discuss the use of fast quantitative 2D NMR strategies to provide accurate quantification of metabolites in targeted metabolomics approaches. Finally, we describe the promising combination of fast 2D NMR methods with hyperpolarization.
Hyperpolarized nuclear magnetic resonance (NMR) offers an ensemble of methods that remarkably address the sensitivity issues of conventional NMR. Dissolution Dynamic Nuclear Polarization (d‐DNP) provides a unique and general way to detect 13C NMR signals with a sensitivity enhanced by several orders of magnitude. The expanding application scope of d‐DNP now encompasses the analysis of complex mixtures at natural 13C abundance. However, the application of d‐DNP in this area has been limited to metabolite extracts. Here, we report the first d‐DNP‐enhanced 13C NMR analysis of a biofluid ‐urine‐ at natural abundance, offering unprecedented resolution and sensitivity for this challenging type of sample. We also show that accurate quantitative information on multiple targeted metabolites can be retrieved through a standard addition procedure.
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