A universal framework for blood ionome extraction and intelligent quality control in ¹H NMR metabolomics
File(s)
Published version
Author(s)
Theodorou, Anastasios
Vučković, Ivan
Papadimitriou, Eirini
Papakonstantinou, Konstantinos
Taki, Vasiliki
Type
Journal Article
Abstract
Nuclear magnetic resonance (NMR) spectroscopy is a cornerstone of metabolomics and clinical bioanalysis; yet, its routine clinical adoption is limited by challenges in quality control (QC) and spectral interpretation. In blood-based NMR studies, ethylenediaminetetraacetic acid (EDTA) and its metal complexes are a major source of spectral interference, obscuring endogenous metabolites while increasing the analytical complexity. Here, we introduce a fully automated cheminformatics platform that enables EDTA-aware QC and the quantitative extraction of metal ion information while preserving metabolic integrity. Using large plasma and serum cohorts acquired at 500 and 600 MHz, we establish a multicenter-validated workflow for accurate quantification of calcium (Ca2+), magnesium (Mg2+), and zinc (Zn2+) directly from routine 1H NMR spectra (R2 > 0.9 versus clinical and spectrometric assays). The platform harmonizes data sets across instruments and cohorts through automated baseline reconstruction. Application to a large breast cancer cohort reveals a stage-dependent decline in circulating Zn2+, consistent with disrupted zinc homeostasis in invasive disease. This work bridges metabolomics and metallomics, advancing the translational utility of NMR in precision medicine.
Date Issued
2026-05-05
Date Acceptance
2026-04-13
Citation
Analytical Chemistry, 2026, 98 (17), pp.12647-12659
ISSN
0003-2700
Publisher
American Chemical Society (ACS)
Start Page
12647
End Page
12659
Journal / Book Title
Analytical Chemistry
Volume
98
Issue
17
Copyright Statement
© 2026 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
License URL
Publication Status
Published
Date Publish Online
2026-04-21