Gadolinium-Based Paramagnetic Relaxation Enhancement Agent Enhances Sensitivity for NUS Multidimensional NMR-Based Metabolomics

Abstract

Gadolinium is a paramagnetic relaxation enhancement (PRE) agent that accelerates the relaxation of metabolite nuclei. In this study, we noted the ability of gadolinium to improve the sensitivity of two-dimensional, non-uniform sampled NMR spectral data collected from metabolomics samples. In time-equivalent experiments, the addition of gadolinium increased the mean signal intensity measurement and the signal-to-noise ratio for metabolite resonances in both standard and plasma samples. Gadolinium led to highly linear intensity measurements that correlated with metabolite concentrations. In the presence of gadolinium, we were able to detect a broad array of metabolites with a lower limit of detection and quantification in the low micromolar range. We also observed an increase in the repeatability of intensity measurements upon the addition of gadolinium. The results of this study suggest that the addition of a gadolinium-based PRE agent to metabolite samples can improve NMR-based metabolomics.

NMR Precision Metabolomics: Dynamic Peak Sum Thresholding and Navigators for Highly Standardized and Reproducible Metabolite Profiling of Clinical Urine Samples

“…Metabolites were analyzed via 1D 1 H and 2D 1 H- 13 C HSQC NMR spectroscopy as previously described [21,22] using a Bruker ASCEND solution-state 600 MHz spectrometer equipped with a liquid helium-cooled Prodigy TCI Cryoprobe (H/F, C, N), using a noesypr1d and hsqcetgpsisp2.2 pulse program with non-uniform sampling (NUS), respectively. All experiments were performed at 298 K with an optimized receiver gain (RG), resulting in an RG of 101 for 2D HSQC spectra.…”

Practical Applications of NMR to Solve Real-World Problems

“…Metabolomics : Honrao and coworkers presented paramagnetic relaxation enhancement (PRE) to increase sensitivity for metabolomics measurements in “ Gadolinium-Based Paramagnetic Relaxation Enhancement Agent Enhances Sensitivity for NUS Multidimensional NMR-Based Metabolomics ” [ 5 ]. By doping reference and test metabolite samples with gadolinium, the authors demonstrated a sensitivity enhancement, especially for the weakest signals, resulting in a lower limit of detection (LOD) and limit of quantification (LOQ).…”