A Giant Leap Forward in Doping Analysis
Maria Parr studies how stored urine samples from athletes can be used to prove that they were taking banned substances even years later.
Apr 21, 2017
Early this year, when the International Olympic Committee (IOC) stripped track and field star Usain Bolt of his gold medal in the 4 × 100-meter relay at the 2008 Beijing Olympics, thereby destroying one of his three legendary “triples,” doping was back in the headlines.
It wasn’t about Bolt himself at all, though; the issue lay with Nesta Carter, one of the other relay runners, who was found to have taken methylhexanamine, a substance related to amphetamine.
Carter was just one of the 98 athletes the doping labs of the World Anti-Doping Agency (WADA) were able to prove had taken banned substances in a follow-up analysis of 1,243 samples taken for the summer games in Beijing and London – after more than eight and four years, respectively.
Most of them had consumed anabolic steroids, which are among the most common performance-enhancing drugs taken by athletes. This class of drugs, artificially derived from the male sex hormone testosterone, is especially popular whenever strength and muscle mass are key.
Maria Parr did seminal research in 2010, laying the foundation to ensure that athletes who had won medals under unfair conditions could still be stripped of those medals years later. Parr, who has been a professor of pharmaceutical and medical chemistry at Freie Universität since 2012, was still working at the WADA lab in Cologne at the time. Now in Berlin, she continues to work on detecting products of the breakdown of banned performance-enhancing substances.
During their new check of the urine samples, doping monitors found various substances. One sample that drew attention was that of Tatyana Lebedeva, who had won the silver medal in the triple jump in Beijing. She had used Oral Turinabol, a synthetic steroid, to enhance her performance.
Oral Turinabol: A Steroid Often Used in East German State-sponsored Doping
And she wasn’t the only one. In an especially striking finding, the monitors found signs of Turinabol abuse in not only the Russian bronze medal winner in the women’s high jump in Beijing, but also in the two next-ranked athletes, one from Russia and one from Ukraine.
“Oral Turinabol was one of the most important performance-enhancing drugs used in the East German state-sponsored doping activities,” Parr explains. It was popular because it was largely unknown at the time, and because it was easy to take orally, in pill form. “After German reunification, Turinabol was thought to have largely disappeared, but it has been making a comeback since 2005, although it is no longer produced legally anywhere.”
Turinabol holds a particular attraction charm from the athletes’ standpoint. As with oxandrolone and stanozolol – two other synthetic steroids that were also found in the current wave of analyses performed by the IOC – it was a long time before researchers knew how this steroid was metabolized in the body. “We knew about a number of products of breaking down Turinabol, but they could only be detected for limited periods,” Parr says.
That changed a few years ago, when Parr and a group of colleagues at the WADA doping lab in Cologne were able to unlock other metabolic products of oxandrolone and Turinabol. In the process, Parr identified a product that had been entirely unknown until then and has a number of structural elements that distinguish it from other known products in chemical terms. Because of its special structure, it spreads differently through the body and can be detected in urine for much longer.
Based on this work, some of Parr’s colleagues at the WADA doping control lab in Moscow landed another coup: They found a previously unknown product of the breakdown of Turinabol that can also be detected in urine for a very long time. This meant WADA suddenly had two new substances it could look for when performing doping tests. And that is just what it did, Parr reports: “It took a little while before the test process was ready to use. But ultimately, the current wave of follow-up analyses is also based on the two metabolic products that we and our colleagues in Moscow described four years ago.”
Like Looking for a Pinch of Sugar in an Olympic-size Swimming Pool
But detecting banned substances is not simple. In normal doping tests, values for several hundred different substances are determined – often in less than 100 milliliters of urine. In the case of anabolic steroids, the experts deal with concentrations on the order of two nanograms per milliliter. For comparison, that is like dissolving a single cube of sugar in a swimming pool with eight 50-meter lanes. In the case of the new metabolites, the concentration is even lower, sometimes by a factor of ten or more. “We’re looking for a pinch of sugar in an Olympic-size swimming pool,” Parr says.
That is another reason further research is needed in order to optimize detection. Right now, Parr’s research group at Freie Universität is working with colleagues from China and Rome, financed through funding provided by WADA, to synthesize the two Turinabol metabolic products. This is because so far, the doping experts only know “their” substances from tests of urine samples using chromatography and mass spectrometry – both methods that can be used to analyze mixtures of substances. There is no powder yet.
But exactly that would be helpful, since it would allow researchers to create reference solutions that could be used for comparative measurements. This would also represent progress for another reason: So far, volunteers have been “doped” with specific amounts of synthetic steroids in order to produce reference urine for measurement purposes. “That isn’t ideal, of course,” Parr says, adding, “The doping control labs would like to move away from that.”
Prof. Dr. Maria Kristina Parr, Freie Universität Berlin, Institute of Pharmacy, Email: firstname.lastname@example.org