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Web End = Metabolomics (2015) 11:17021707 DOI 10.1007/s11306-015-0828-1
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Web End = Quantication of 1H NMR spectra from human plasma
Robin A. de Graaf1,5 Hetty Prinsen1 Cosimo Giannini2 Sonia Caprio3
Raimund I. Herzog4
Received: 13 March 2015 / Accepted: 27 June 2015 / Published online: 5 July 2015 Springer Science+Business Media New York 2015
Abstract Human plasma is a biouid that is high in information content, making it an excellent candidate for metabolomic studies. 1H NMR has been a popular technique to detect several dozen metabolites in blood plasma. In order for 1H NMR to become an automated, high-throughput method, challenges related to (1) the large signal from lipoproteins and (2) spectral overlap between different metabolites have to be addressed. Here diffusion-weighted 1H NMR is used to separate lipoprotein and metabolite signals based on their large difference in translational diffusion. The metabolite 1H NMR spectrum is then quantied through spectral tting utilizing full prior knowledge on the metabolite spectral signatures. Extension of the scan time by 3 min or 15 % per sample allowed the acquisition of a 1H NMR spectrum with high diffusion weighting. The metabolite 1H NMR spectra could reliably be modeled with 28 metabolites. Excellent correlation was
found between results obtained with diffusion NMR and ultraltration. The combination of minimal sample preparation together with minimal user interaction during processing and quantication provides a metabolomics technique for automated, quantitative 1H NMR of human plasma.
Keywords Human plasma 1H NMR Diffusion
Spectral quantication Lipoproteins
1 Introduction
Human plasma is a biouid that is high in information content, making it an excellent candidate for metabolomic studies (Psychogios et al. 2011). Besides mass spectrometry (MS)-based methods, 1H NMR has been a popular technique to detect several dozen metabolites in blood plasma. However, in order to become a quantitative and high-throughput method 1H NMR has several challenges to overcome. Firstly, the bulk of signal intensity in a typical
1H NMR spectrum arises from lipoproteins, which complicate the detection and quantication of metabolites. Traditionally, lipoproteins are removed by ultraltration (Wevers et al....