Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies
Frank Klont,
Piotr Sosnowski,
Daan Kremer,
Tim J. Knobbe,
Ron Bonner,
Hans Blokzijl,
Rinse K. Weersma,
Stephan J. L. Bakker,
TransplantLines Investigators,
Eelko Hak,
Daan J. Touw,
Gérard Hopfgartner
Affiliations
Frank Klont
Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest Ansermet 24, 1211 Geneva, Switzerland
Piotr Sosnowski
Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest Ansermet 24, 1211 Geneva, Switzerland
Daan Kremer
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Tim J. Knobbe
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Ron Bonner
Ron Bonner Consulting, Newmarket, ON L3Y 3C7, Canada
Hans Blokzijl
Department of Gastroenterology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Rinse K. Weersma
Department of Gastroenterology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Stephan J. L. Bakker
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
TransplantLines Investigators
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
Eelko Hak
Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
Daan J. Touw
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Gérard Hopfgartner
Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest Ansermet 24, 1211 Geneva, Switzerland
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.
