title: Investigation of urinary excretion of hydroxyethyl starch and dextran by uhplc-hrms in different acquisition modes.
abstract: Plasma volume expanders (PVEs) such as hydroxyethyl starch (HES) and dextran are misused in sports because they can prevent dehydration and reduce haematocrit values to mask erythropoietin abuse. Endogenous hydrolysis generates multiple HES and dextran oligosaccharides which are excreted in urine. Composition of the urinary metabolic profiles of PVEs varies depending on post-administration time and can have an impact on their detectability. In this work, different mass spectrometry data acquisition modes (full scan with and without in-source collision-induced dissociation) were used to study urinary excretion profiles of HES and dextran, particularly by investigating time-dependent detectability of HES and dextran urinary oligosaccharide metabolites in post-administration samples. In-source fragmentation yielded the best results in terms of limit of detection (LOD) and detection times, whereas detection of HES and dextran metabolites in full scan mode with no in-source fragmentation is related to recent administration (< 24 hours). Urinary excretion studies showed detection windows for HES and dextran respectively of 72 and 48 hours after administration. Dextran concentrations were above the previously proposed threshold of 500 µg · mL(-1) for 12 hours. A "dilute-and-shoot" method for the detection of HES and dextran in human urine by ultra-high-pressure liquid chromatography-electrospray ionization-high resolution Orbitrap™ mass spectrometry was developed for this study. Validation of the method showed an LOD in the range of 10-500 µg · mL(-1) for the most significant HES and dextran metabolites in the different modes. The method allows retrospective data analysis and can be implemented in existing high-resolution mass spectrometry-based doping control screening analysis.
authors.affiliation: Doping Control Laboratory, Ghent University (UGent), Technologiepark 30, 9052 Zwijnaarde, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Esposito
authors.affiliation: Doping Control Laboratory, Ghent University (UGent), Technologiepark 30, 9052 Zwijnaarde, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Deventer
authors.affiliation: Department of Analytical Chemistry, University of Extremadura, Avda.deElvas s/n, 06006 Badajoz, Spain.
authors.forename: A J
authors.initials: AJ
authors.lastname: Giron
authors.affiliation: Doping Control Laboratory, Ghent University (UGent), Technologiepark 30, 9052 Zwijnaarde, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Roels
authors.affiliation: Department of Anesthesia, Ghent University Hospital, De Pintelaan 185, 9000 Gent Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Herregods
authors.affiliation: Department of Clinical Biology, microbiology and immunology, Ghent University Hospital, De Pintelaan 185, 9000 Gent Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Verstraete
authors.affiliation: Doping Control Laboratory, Ghent University (UGent), Technologiepark 30, 9052 Zwijnaarde, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Van Eenoo
keywords: Dextran; LC-HRMS; Orbitrap; doping; hydroxyethyl starch; plasma volume expanders