Incorporating cutting-edge analytical science research into anti-doping testing

Abstract

Seven years ago, in July 2005, London was awarded the Games of the XXX Olympiad. I was privileged to be a member of the bid team during its presentation to the International Olympic Committee (IOC) in February of that year. Once the Games had been awarded, the race was on to ensure that everything required would be in place in time. As Director of the Drug Control Centre, finding suitable laboratory space was the first challenge for me. After a year of fruitless searching, we discovered that GlaxoSmithKline (GSK) was shutting down part of its Harlow facility. Discussions with GSK were successful because of our common aim to help protect the integrity of the Games and the health of the athletes. Thankfully, the Harlow site was agreed as the centre of operations for all anti-doping analysis during the Games. My next task was to deliver a world-class anti-doping service. The IOC follows the rules published by the World Anti-Doping Agency (WADA), to which athletes competing in the Games and WADA accredited laboratories must adhere. Following the IOC motto of “Citius, Altius, Fortius”, I decided that this would be an appropriate strategy to ensure faster analysis with higher sensitivity, and stronger proof in cases of doping. A number of new analytical methods were developed as exemplified in this Editorial. Faster analysis was obtained with excellent sensitivity using a modified gas chromatography–tandem mass spectrometry (GC–MS/ MS) screening method. After extensive development and optimisation, we reduced our run-times from 40 min to 14 min using short capillary GC columns. This GC–MS/MS screen was complemented with an ultra high pressure chromatography (UHPLC) with high resolution mass spectrometry (HRMS) screen. Although HRMS has been used since the Summer Olympic Games in Atlanta in 1996, it has always been used in selected ion monitoring mode for its excellent sensitivity, but only for a relatively small number of analytes. For the firsttime, and after much research, we concluded that we could reliably use UHPLCwithHRMStoscreenforover200analytes. Thisneededboth positive and negative ionisation modes together with collision induced dissociation with all three MS experiments occurring rapidly so as not to compromise chromatographic performance. Working in full scan mode, the volume of data we acquired was enormous and review of the vast amount of data was our next challenge. After extensive collaborationwith the manufacturer and many, manyrevisions, we now have software that will identify the targeted analytes in 2 min after a 10 min acquisition time. Any new designer substance can now be readily searched for since we are working in full scan mode. Furthermore, now that multiple samples are collected from a single athlete over time (theathlete biological passport)we can review suchdata to search for any change in biomarkers. Indeed, as the electronic files, like the samples, are stored for 8 years, it will now be possible to review the data at a later date to confirm that no prohibited substance had been taken at the time of sample collection.