{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:49:50Z","timestamp":1792511390063,"version":"4.5.0"},"reference-count":76,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>As end-products of the intersection between the genome and environmental influences, metabolites represent a promising approach to the discovery of novel biomarkers for diseases. However, many potential biomarker candidates identified by metabolomics studies fail to progress beyond analytical validation for routine implementation in clinics. Awareness of the challenges present can facilitate the development and advancement of innovative strategies that allow improved and more efficient applications of metabolite-based markers in clinical settings. This minireview provides a comprehensive summary of the pre-analytical factors, required analytical validation studies, and kit development challenges that must be resolved before the successful translation of novel metabolite biomarkers originating from research. We discuss the necessity for strict protocols for sample collection, storage, and the regulatory requirements to be fulfilled for a bioanalytical method to be considered as analytically validated. We focus especially on the blood as a biological matrix and liquid chromatography coupled with tandem mass spectrometry as the analytical platform for biomarker validation. Furthermore, we examine the challenges of developing a commercially viable metabolomics kit for distribution. To bridge the gap between the research lab and clinical implementation and utility of relevant metabolites, the understanding of the translational challenges for a biomarker panel is crucial for more efficient development of metabolomics-based precision medicine.<\/jats:p>","DOI":"10.3390\/metabo14040200","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T03:37:21Z","timestamp":1712115441000},"page":"200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Challenges in the Metabolomics-Based Biomarker Validation Pipeline"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5077-4161","authenticated-orcid":false,"given":"Shenghan","family":"Li","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Psoriatic Arthritis Program, Schroeder Arthritis Program, University Health Network, Toronto, ON M5T 0S8, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Looby","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Psoriatic Arthritis Program, Schroeder Arthritis Program, University Health Network, Toronto, ON M5T 0S8, Canada"},{"name":"Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, Canada"},{"name":"Division of Orthopaedic Surgery, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, ON M5T 0S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Chandran","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Psoriatic Arthritis Program, Schroeder Arthritis Program, University Health Network, Toronto, ON M5T 0S8, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, Canada"},{"name":"Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5610-873X","authenticated-orcid":false,"given":"Vathany","family":"Kulasingam","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Division of Clinical Biochemistry, Laboratory Medicine Program, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/1535370217750088","article-title":"Biomarker Definitions and Their Applications","volume":"243","author":"Califf","year":"2018","journal-title":"Exp. 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