Simultaneous detection of xenon and krypton in equine plasma by gas chromatography-tandem mass spectrometry for doping control

Xenon can activate the hypoxia-inducible factors (HIFs). As such, it has been allegedly used in human sports for increasing erythropoiesis. Krypton, another noble gas with reported narcosis effect, can also be expected to be a potential and less expensive erythropoiesis stimulating agent. This has raised concern about the misuse of noble gases as doping agents in equine sports. The aim of the present study is to establish a method for the simultaneous detection of xenon and krypton in equine plasma for the purpose of doping control. Xenon- or krypton-fortified equine plasma samples were prepared according to reported protocols. The target noble gases were simultaneously detected by gas chromatography-triple quadrupole mass spectrometry using headspace injection. Three xenon isotopes at m/z 129, 131, and 132, and four krypton isotopes at m/z 82, 83, 84, and 86 were targeted in selected reaction monitoring mode (with the precursor ions and product ions at identical mass settings), allowing unambiguous identification of the target analytes. Limits of detection for xenon and krypton were about 19 pmol/mL and 98 pmol/mL, respectively. Precision for both analytes was less than 15%. The method has good specificity as background analyte signals were not observed in negative equine plasma samples (n = 73). Loss of analytes under different storage temperatures has also been evaluated.