Interlaboratory Reproducibility of a Targeted Metabolomics Platform for Analysis of Human Serum and Plasma
Open accessAbstract
A critical question facing the field of metabolomics is whether data obtained from different centers can be effectively compared and combined. An important aspect of this is the interlaboratory precision (reproducibility) of the analytical protocols used. We analyzed human samples in six laboratories using different instrumentation but a common protocol (the AbsoluteIDQ p180 kit) for the measurement of 189 metabolites via liquid chromatography (LC) or flow injection analysis (FIA) coupled to tandem mass spectrometry (MS/MS). In spiked quality control (QC) samples 82% of metabolite measurements had an interlaboratory precision of <20%, while 83% of averaged individual laboratory measurements were accurate to within 20%. For 20 typical biological samples (serum and plasma from healthy individuals) the median interlaboratory coefficient of variation (CV) was 7.6%, with 85% of metabolites exhibiting a median interlaboratory CV of <20%. Precision was largely independent of the type of sample (serum or plasma) or the anticoagulant used but was reduced in a sample from a patient with dyslipidaemia. The median interlaboratory accuracy and precision of the assay for standard reference plasma (NIST SRM 1950) were 107% and 6.7%, respectively. Likely sources of irreproducibility were the near limit of detection (LOD) typical abundance of some metabolites and the degree of manual review and optimization of peak integration in the LC-MS/MS data after acquisition. Normalization to a reference material was crucial for the semi-quantitative FIA measurements. This is the first interlaboratory assessment of a widely used, targeted metabolomics assay illustrating the reproducibility of the protocol and how data generated on different instruments could be directly integrated in large-scale epidemiological studies.
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The targeted metabolomics approach used is quantitative and reliable and can be more readily confirmed and validated in other laboratories compared with whole-metabolome analyses.
“While our targeted approach is restrictive in that regard, it is quantitative and reliable (39) and, compared with whole-metabolome analyses, can be more readily confirmed and validated in other laboratories.”
From Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism (2018) · cites this paper as [39]
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Flagged first, then by citations
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- Authors
- Siskos, A. P., Jain, P., Römisch-Margl, W., Bennett, M., Achaintre, D., Asad, Y., Marney, L., Richardson, L., Koulman, A., Griffin, J. L., Raynaud, F., Scalbert, A., Adamski, J., Prehn, C., & Keun, H. C.
- Affiliations
- Imperial College London (GB)
- Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany
- Centre international de recherche sur le cancer (FR)
- Institute of Cancer Research (GB)
- MRC Elsie Widdowson Laboratory (GB)
- Helmholtz Munich (DE)
- Corresponding author
- Keun, Hector C.
- ORCID
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-12-13
- Volume
- 89
- Issue
- 1
- Pages
- 656-665
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- PMC
- PMC6317696
- OpenAlex
- W2558872626
- Cited by
- 269
- References
- 36
- Citations by year
- 2026: 24 · 2025: 19 · 2024: 22 · 2023: 30 · 2022: 26 · 2021: 39 · 2020: 40 · 2019: 26 · 2018: 26 · 2017: 17
- FWCI
- 11.96
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Apollo
- Funders
- Medical Research Council (MC_PC_13030, MC_PC_13046, MC_UP_A090_1006)
- Seventh Framework Programme (259867, 266838, 602156, 603864)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Scientific Measurement and Uncertainty Evaluation
- Keywords
- interlaboratory reproducibility, targeted metabolomics, human serum, human plasma, LC-MS/MS, flow injection analysis, coefficient of variation, quality control samples, NIST SRM 1950, peak integration, dyslipidemia, detection limit
- MeSH terms
- Humans, Laboratories, Quality Control, Reference Standards, Reproducibility of Results, Tandem Mass Spectrometry, Metabolomics, Limit of Detection
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