title: The atypical excretion profile of meldonium: Comparison of urinary detection windows after single- and multiple-dose application in healthy volunteers.
abstract: Following a one-year monitoring program providing unequivocal analytical evidence for a high prevalence in international elite sports, meldonium has been included in the World Anti-Doping Agency's (WADA) list of prohibited substances that came into effect on 1 January 2016. Despite of the polar and hydrophilic nature of the molecule, an unusual long detection window was observed in pilot elimination studies. Consequently, in the present study, urinary excretion profiles after single-dose (5 volunteers, 1×500mg) and multiple-dose oral application (5 volunteers; 2×500mg/day for 6days) were determined in order to facilitate the result management concerning meldonium findings in doping controls. Particularly the option to differentiate between recent use and tapering concentrations was studied. Urinary meldonium concentrations were determined using an analytical approach based on hydrophilic interaction liquid chromatography and high resolution tandem mass spectrometry. The study corroborates the hypothesis of a non-linear, dose-depended and biphasic excretion profile after oral application of meldonium and demonstrates that urinary detection windows are of considerable extent with up to 65 and 117days (concentrations>LOQ of 10ng/mL) following single- and multiple-dose applications, respectively.
authors.affiliation: Institute of Biochemistry, Center for Preventive Doping Research, German Sport University, Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Görgens
authors.affiliation: Institute of Biochemistry, Center for Preventive Doping Research, German Sport University, Cologne, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Guddat
authors.affiliation: Institute of Biochemistry, Center for Preventive Doping Research, German Sport University, Cologne, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Bosse
authors.affiliation: Institute of Biochemistry, Center for Preventive Doping Research, German Sport University, Cologne, Germany; European Monitoring Center for Emerging Doping Agents (EuMoCEDA), Cologne, Bonn, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Geyer
authors.affiliation: Romanian Doping Control Laboratory, National Anti-Doping Agency, Bvd. Basarabia, nr. 37-39, Bucharest, Romania.
authors.forename: Valentin
authors.initials: V
authors.lastname: Pop
authors.affiliation: Institute of Biochemistry, Center for Preventive Doping Research, German Sport University, Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schänzer
authors.affiliation: Institute of Biochemistry, Center for Preventive Doping Research, German Sport University, Cologne, Germany; European Monitoring Center for Emerging Doping Agents (EuMoCEDA), Cologne, Bonn, Germany. Electronic address: thevis@dshs-koeln.de.
authors.forename: Mario
authors.initials: M
authors.lastname: Thevis
mesh_terms: D000328:Adult; D001826:Body Fluids / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods; D004300:Doping in Sports / Q000379:methods; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008763:Methylhydrazines / Q000652:urine*; D008875:Middle Aged; D013177:Sports; D015813:Substance Abuse Detection / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate
keywords: Doping; HILIC; Mass spectrometry; Mildronate; Sport