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May 18, 2026Metabolomics0 citationsOpen Access

Benchmarking untargeted metabolomics data quality with allopurinol-induced perturbations

TVTerje VasskogPHPia J. HeinsvigESEkaterina Sharashova

Key Points

  • This research aims to determine if drug-induced metabolic changes can serve as internal benchmarks for assessing metabolomics dataset quality.
  • Analyzed 1,000 serum samples from the TROMBOLOME study using targeted and untargeted metabolomics panels.
  • Classified 19 samples as allopurinol-positive based on specific analytical targets.
  • Performed statistical evaluations using Mann–Whitney U-tests.
  • Found significant upregulation of xanthine, orotate, and orotidine in allopurinol-positive cases (p < 0.0001).
  • Demonstrated reproducibility of metabolic perturbations within the dataset.

Abstract

Abstract Introduction We present a simple test to assess whether a metabolomics dataset is fit-for-purpose. Current qualitycontrol approaches do not directly evaluate the ability to recover biologically meaningful perturbations. Objectives To evaluate whether known drug-induced metabolic perturbations can serve as internal benchmarks fordataset quality. Methods In a study (the TROMBOLOME study, unrelated to allopurinol therapy), 1,000 serum samples were analyzedwith one targeted and two untargeted metabo lomics panels. Samples were classified as allopurinol-positive (N=19)using detection of allopurinol analytical targets. Endogenous metabolite markers of allopurinol therapy wereevaluated based on hypotheses derived from the literature. Statistical evaluation was performed using Mann–Whitney U-tests. Results The hypothesis of upregulation was supported for xanthine, orotate, and orotidine (p < 0.0001) inallopurinol-positive cases (N = 19). These findings demonstrate repro ducibility of well-characterized metabolicperturbations within the dataset. Conclusion In the absence of external quality assessment schemes for untargeted metabolomics, such benchmarkscould provide a practical way to evaluate whether datasets are suitable for downstream biological interpretation.The proposed targeted exposomics approach complements traditional QC metrics by assessing biologicalrecoverability.

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Cite This Study

Vasskog et al. (2026) studied this question.

synapsesocial.com/papers/6a0aad015ba8ef6d83b706d2https://doi.org/10.1007/s11306-026-02457-x
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