Dried Blood Spots + NMR = True

Exploring nuclear magnetic resonance spectroscopy for the analysis of dried blood spots

Cristina Alexandrescu, Sander Johannes Thorbjørnsen Guttorm , Katja Benedikte Prestø Elgstøen, Frode Rise, Steven Ray Wilson (corresponding author)

The study by Alexandrescu et al. (2025) explores the feasibility of using ^1H NMR spectroscopy to analyze dried blood spots (DBS) for metabolomic profiling. DBS sampling has long been used in newborn screening and clinical assays due to its minimal invasiveness, low sample volume, and ease of storage and transport. However, its potential in metabolomics has mainly been explored with mass spectrometry, while NMR has received little attention. The authors aimed to optimize conditions that would make DBS compatible with NMR analysis and evaluate its robustness under real-world transport conditions.

They systematically tested extraction strategies, comparing aqueous and methanol-based solvents, while also evaluating parameters such as extraction time, number of punches, and suppression of interfering macromolecular signals. Methanol extraction proved superior, giving higher metabolite recovery and cleaner spectra compared to aqueous buffers. The authors also documented contamination signals originating from sampling consumables, which is important to account for in order to avoid misinterpretation.

As a proof of concept, DBS cards were shipped both locally and internationally before analysis. Despite some variation in the resulting spectra, the metabolic profiles retained individual-specific signatures, suggesting that DBS–NMR can be a robust tool even when samples undergo handling and transport.

Overall, the work demonstrates that NMR spectroscopy can be applied to DBS analysis, complementing mass spectrometry by offering high reproducibility and simple sample handling, even if sensitivity is lower. This proof-of-concept study highlights a pathway for broader use of DBS–NMR in metabolomics, particularly for comparative or large-scale studies.