{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T13:31:58Z","timestamp":1792848718900,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the European Union\u2019s Horizon 2020 research and innovation program","award":["887661"],"award-info":[{"award-number":["887661"]}]},{"name":"Astellas Pharma B.V.","award":["887661"],"award-info":[{"award-number":["887661"]}]},{"name":"Chiesi Pharmaceuticals B.V.","award":["887661"],"award-info":[{"award-number":["887661"]}]},{"name":"the Dutch Ministry of Economic Affairs and Climate Policy","award":["887661"],"award-info":[{"award-number":["887661"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Mass spectrometry (MS) is increasingly used in clinical studies to obtain molecular evidence of chemical exposures, such as tobacco smoke, alcohol, and drugs. This evidence can help verify clinical data retrieved through anamnesis or questionnaires and may provide insights into unreported exposures, for example those classified as the same despite small but possibly relevant chemical differences or due to contaminants in reported exposure compounds. Here, we aimed to explore the potential of untargeted SWATH metabolomics to differentiate such closely related exposures. This data-independent acquisition MS-based profiling technique was applied to urine samples of 316 liver and 570 kidney transplant recipients from the TransplantLines Biobank and Cohort Study (NCT03272841), where we focused on the immunosuppressive drug mycophenolate, which is either supplied as a morpholino-ester prodrug or as an enteric-coated product, the illicit drug cocaine, which is usually supplied as an adulterated product, and the proton pump inhibitors omeprazole and esomeprazole. Based on these examples, we found that untargeted SWATH metabolomics has considerable potential to identify different (unreported) exposure or co-exposure metabolites and may determine variations in their abundances. We also found that these signals alone may sometimes be unable to distinguish closely related exposures, and enhancement of differentiation, for example by integration with pharmacogenomics data, is needed.<\/jats:p>","DOI":"10.3390\/metabo12100942","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T04:00:02Z","timestamp":1665288002000},"page":"942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3503-1694","authenticated-orcid":false,"given":"Frank","family":"Klont","sequence":"first","affiliation":[{"name":"Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest Ansermet 24, 1211 Geneva, Switzerland"},{"name":"Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands"},{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4261-269X","authenticated-orcid":false,"given":"Piotr","family":"Sosnowski","sequence":"additional","affiliation":[{"name":"Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest Ansermet 24, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0011-115X","authenticated-orcid":false,"given":"Daan","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3246-3192","authenticated-orcid":false,"given":"Tim J.","family":"Knobbe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0532-8323","authenticated-orcid":false,"given":"Ron","family":"Bonner","sequence":"additional","affiliation":[{"name":"Ron Bonner Consulting, Newmarket, ON L3Y 3C7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4240-7506","authenticated-orcid":false,"given":"Hans","family":"Blokzijl","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinse K.","family":"Weersma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-6791","authenticated-orcid":false,"given":"Stephan J. L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TransplantLines","family":"Investigators","sequence":"additional","affiliation":[{"name":"Group of Authors on Behalf of the Transplant Lines Biobank and Cohort Study, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eelko","family":"Hak","sequence":"additional","affiliation":[{"name":"Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-4789","authenticated-orcid":false,"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"},{"name":"Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Hopfgartner","sequence":"additional","affiliation":[{"name":"Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest Ansermet 24, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/00333549141291S206","article-title":"The social determinants of health: It\u2019s time to consider the causes of the causes","volume":"129","author":"Braveman","year":"2014","journal-title":"Public Health Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.bbadis.2014.06.015","article-title":"Next generation sequencing technology: Advances and applications","volume":"1842","author":"Buermans","year":"2014","journal-title":"Biochim. 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