Last Month's Most Accessed Feature: Xenon in doping control: A rare gas blood test

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  • Published: Jul 10, 2014
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Xenon blood doping

Xenon has just been placed on the prohibited list of doping compounds by WADA just as a novel method for measuring it in blood and plasma by GC/MS has been announced.

The World Anti-Doping Agency has its work cut out trying to keep up with the drugs cheats and their "advisers" who come up with more ingenious ways to increase performance and dodge detection. But two substances that have just been added to the prohibited list appear out of place to the usual types of steroids and performance-enhancing substances. They are the rare gases argon and xenon, which could be used to boost levels of the hormone erythropoietin (EPO) which, in turn stimulates the production of red blood cells.

The use of xenon by athletes is controversial. When breathed in, it promotes formation of the protein Hif1-alpha, which signals the body to increase production of several proteins, including EPO. Under WADA regulations, boosting the levels of EPO by injecting EPO itself or taking Hif1-alpha stabilisers is illegal.

However, there are those who argue that breathing xenon is no different to training at altitude to stimulate red blood cell production. This is the case in Russia, where government authorities issued guidelines for taking xenon before competition, in order to get a smoother sleep, reduce tiredness and improve recovery after exercise. In fact, it is widely believed that Russian athletes have been using xenon from the Athens Olympics in 2004 to the Sochi winter games this year.

WADA has given the national anti-doping organizations 90 days to implement the change and, in a timely intervention, scientists have just published a new method to measure xenon in humans which would help accredited labs to run detection tests. The GC/MS procedure is also appropriate for doping control samples collected under the conventional Athlete Biological Passport guidelines.

Isotopic identification

The people involved work at centres of drug doping research in Germany. Mario Thevis, Wilhelm Schänzer and colleagues from the Center for Preventive Doping Research at the German Sport University Cologne, the European Monitoring Center for Emerging Doping Agents (EuMoCEDA), Cologne/Bonn, and University Hospital Düsseldorf explained their method in Rapid Communications in Mass Spectrometry.

It was developed by detecting three major isotopes of xenon at m/z values of 128.9048, 130.9045 and 131.9042 on a high-resolution GC-time-of-flight instrument. Plasma was fortified with 500 nmol/mL xenon and incubated in an autosampler vial to release the gas into the headspace for subsequent injection onto the GC column.

In practice, the column was not important and the retention time information was irrelevant because the gas showed no interaction with the GC phase. Nonetheless, the precision was acceptable at 18.7% for 50 nmol/mL and 3.8% for 500 nmol/mL xenon even without the use of an internal standard.

The detection limit was 50 nmol/mL plasma, but when the method was transferred to a triple quadrupole system commonly found in doping control labs, the limit fell to 0.5 nmol/mL. This level "opens up opportunities for improving detection windows in a doping control context," said the research team. One potential source of interference is the xenon present in air, which is typically 87 nL/L air (87 ppb) but this is well below the detection limits of the instruments, so would have no effect in tests.

Athlete Biological Passport

Xenon is used as a modern anaesthetic, so the team acquired pre- and post-operative blood samples from a patient undergoing xenon-supported anaesthesia with which to test their method. The samples were held in sealed containers at 4-8°C and analysed 18-30 hours after collection. Xenon was detected unequivocally within this timescale, which fits with the requirements of the testing program. By the same token, the results confirm that routine samples taken for testing in accordance with the Athlete Biological Passport can be used to look for xenon too.  

The next step, according to Thevis, is to investigate the effects of different xenon doses which can be administered by varying the exposure time or the proportion of xenon in the gas mixture to be breathed in. In addition, the sampling and storage procedures, which appeared to be adequate in this testing phase, should also be examined to ensure that the best methods are in place.

The great advantage of this method, once validated, is that it can be carried out on the types of samples already collected for drug control, on equipment that is in place in drug testing labs, within the guidelines for the Athlete Biological Passport.

Related Links

Rapid Communications in Mass Spectrometry 2014, 28, 1501-1506: "Measuring xenon in human plasma and blood by gas chromatography/mass spectrometry"

Article by Steve Down

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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