A proposed framework to evaluate the quality and reliability of targeted metabolomics assays from the UK Consortium on Metabolic Phenotyping (MAP/UK)

Sarir Sarmad, Mark R Viant, Warwick B Dunn, Royston Goodacre, Ian D Wilson, Katie E Chappell, Jules Griffin, Valerie B O'Donnell, Brendon Naicker, Matthew R Lewis, Toru Suzuki* (Corresponding Author), UK Consortium on Metabolic Phenotyping (MAP/UK)

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)


Targeted metabolite assays that measure tens or hundreds of pre-selected metabolites, typically using liquid chromatography-mass spectrometry, are increasingly being developed and applied to metabolic phenotyping studies. These are used both as standalone phenotyping methods and for the validation of putative metabolic biomarkers obtained from untargeted metabolomics studies. However, there are no widely accepted standards in the scientific community for ensuring reliability of the development and validation of targeted metabolite assays (referred to here as 'targeted metabolomics'). Most current practices attempt to adopt, with modifications, the strict guidance provided by drug regulatory authorities for analytical methods designed largely for measuring drugs and other xenobiotic analytes. Here, the regulatory guidance provided by the European Medicines Agency, US Food and Drug Administration and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use are summarized. In this Perspective, we have adapted these guidelines and propose a less onerous 'tiered' approach to evaluate the reliability of a wide range of metabolomics analyses, addressing the need for community-accepted, harmonized guidelines for tiers other than full validation. This 'fit-for-purpose' tiered approach comprises four levels-discovery, screening, qualification and validation-and is discussed in the context of a range of targeted and untargeted metabolomics assays. Issues arising with targeted multiplexed metabolomics assays, and how these might be addressed, are considered. Furthermore, guidance is provided to assist the community with selecting the appropriate degree of reliability for a series of well-defined applications of metabolomics.

Original languageEnglish
Pages (from-to)1017-1027
Number of pages11
JournalNature Protocols
Early online date24 Feb 2023
Publication statusPublished - 1 Apr 2023

Bibliographical note

Funding was provided by the Medical Research Council (grant reference: MR/
S010483/1) to the MAP/UK project. Wellcome Trust provided support for LIPID
MAPS (203014/Z/16/Z) to V.B.O’D.

Data Availability Statement

Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41596-022008018


  • mass spectrometry
  • Metabolomics


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