title: Urine analysis concerning xenon for doping control purposes.
abstract: BACKGROUND
  On September 1(st) 2014, a modified Prohibited List as established by the World Anti-Doping Agency (WADA) became effective featuring xenon as a banned substance categorized as hypoxia-inducible factor (HIF) activator. Consequently, the analysis of xenon from commonly provided doping control specimens such as blood and urine is desirable, and first data on the determination of xenon from urine in the context of human sports drug testing, are presented.
  
  
  METHODS
  In accordance to earlier studies utilizing plasma as doping control matrix, urine was enriched to saturation with xenon, sequentially diluted, and the target analyte was detected as supported by the internal standard d6 -cyclohexanone by means of gas chromatography/triple quadrupole mass spectrometry (GC/MS/MS) using headspace injection. Three major xenon isotopes at m/z 128.9, 130.9 and 131.9 were targeted in (pseudo) selected reaction monitoring mode enabling the unambiguous identification of the prohibited substance. Assay characteristics including limit of detection (LOD), intraday/interday precision, and specificity as well as analyte recovery under different storage conditions were determined. Proof-of-concept data were generated by applying the established method to urine samples collected from five patients before, during and after (up to 48 h) xenon-based general anesthesia.
  
  
  RESULTS
  Xenon was traceable in enriched human urine samples down to the detection limit of approximately 0.5 nmol/mL. The intraday and interday imprecision values of the method were found below 25%, and specificity was demonstrated by analyzing 20 different blank urine samples that corroborated the fitness-for-purpose of the analytical approach to unequivocally detect xenon at non-physiological concentrations in human urine. The patients' urine specimens returned 'xenon-positive' test results up to 40 h post-anesthesia, indicating the limits of the expected doping control detection window.
  
  
  CONCLUSIONS
  Since xenon has been considered a prohibited substance according to WADA regulations in September 2014, its analysis from common specimens of routine sports drug testing is desirable. In previous studies, its traceability in whole blood and plasma was shown, and herein a complementary approach utilizing doping control urine samples for the GC/MS/MS analysis of xenon was reported.
authors.affiliation: Center for Preventive Doping Research - Institute of Biochemistry, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany; European Monitoring Center for Emerging Doping Agents (EuMoCEDA), Cologne/Bonn, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Thevis
authors.forename: Thomas
authors.initials: T
authors.lastname: Piper
authors.forename: Hans
authors.initials: H
authors.lastname: Geyer
authors.forename: Maximilian S
authors.initials: MS
authors.lastname: Schaefer
authors.forename: Julia
authors.initials: J
authors.lastname: Schneemann
authors.forename: Peter
authors.initials: P
authors.lastname: Kienbaum
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schänzer
mesh_terms: D000368:Aged; D004300:Doping in Sports; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014978:Xenon / Q000652:urine*
chemical_list: D014978:Xenon