SULM – Schweizerische Union für Labormedizin | Union Suisse de Médecine de Laboratoire | Swiss Union of Laboratory Medicine

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CéDRIC BOVET1, LIA BALLY2, THOMAS ZUEGER2, CHRISTOS NAKAS1, JEAN-MARC NUOFFER1, MARTIN FIEDLER1, ALEXANDER LEICHTLE1, CHRISTOPH STETTLER2

1University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland, 2Division of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, Bern University Hospital, Bern, Switzerland

Nowadays, ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) achieves broad metabolome coverage in biological matrices. For a clinical laboratory, combining UHPLC-MS with the large set of clinical assays could accelerate the discovery and validation of metabolic signatures.

To assess this potential, we established a complete analytical workflow for the metabolic profiling of plasma, serum, urine and tissue by high-resolution UHPLC-MS (UPLC coupled to Synapt G2-S HDMS Q-TOF, Waters). The broad polarity of metabolites can be assessed by reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC). By using RPLC, we successfully discovered exercise-related metabolic differences between intermittent high intensity exercise (IHE) and iso-energetic continuous moderate intensity exercise (CONT) in individuals with well-controlled type 1 diabetes. Discriminant analysis of the 2534 detected features in serum suggested that the purine metabolism, cortisol and acylcarnitines were significantly regulated at 80 min of exercise and 120 min post-exercise compared to baseline with significant differences between IHE and CONT. The variations in the profiles of metabolites were then validated with clinical assays routinely used in our laboratory. Purine metabolites (i.e., hypoxanthine and uric acid) and cortisol were quantified on a clinical chemistry analyzer (Cobas 8000, Roche), acylcarnitines on a triple quadrupole mass spectrometer (UPLC coupled to Xevo TQ-S, Waters). Our results demonstrated that clinical laboratories could benefit from the synergy existing between UHPLC-MS and conventional clinical assays. Their combination offers an efficient panel for discovering regulated pathways, thereby strengthening multidisciplinary collaborations and translational research.

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