Dr. Thevis, (PhD, GTFCh), the anti-doping scientist and professor from Germany, speaks with the PCC about his Mildronate study, choosing the anti-doping discipline, and what’s next on his radar. 

What got you started in anti-doping research?
I was a third year chemistry student at the University of Aachen when I started a student job in pesticide residue analysis, which triggered my interest in analytical chemistry. As I was also a sports science student at the time,
I took advantage of an opportunity to combine my interest in both sport and chemistry through pursuing a PhD in anti-doping research under the supervision of Professor Schänzer.

How did you first engage with the PCC? 
When the PCC initiative was started in 2008, it was greatly appreciated among anti-doping scientists. Historically, funding opportunities have been limited for this specialized field of research. My team and I had been actively looking for organizations such as the PCC that could be partners and sponsors of
our anti-doping efforts. We’re happy to report several successful applications thus far.

What intrigued you about Mildronate? What prompted research into the substance? 
Mildronate (or Meldonium) was found in the possession of athletes about 10 years ago. Since then, the substance’s
relevance to doping controls was questioned sporadically, but information
remained scarce. In 2013/2014, testing procedures applied to routine doping control samples indicated the presence of a compound in substantial abundance in a series of urine specimens. As the compound could interfere with the measurement of other known analytes, my team investigated further. The compound turned out to be Meldonium, and with the use of improved instrumental
testing options, monitoring was facilitated, followed by explicit testing.

Can you tell us a bit about the scientific process of your research? 
Mildronate is of low molecular mass and due to its composition and structure, a rather polar analyte. These
properties are not ideal when using common testing methods, which rely heavily upon chromatographic mass spectrometric approaches. However, my team was able to modify a routine test method and establish a
dedicated confirmatory assay by using an in-house synthesized stable isotope-labelled internal standard hyrophilic liquid chromatography (HILIC) coupled with high resolution/high accuracy tandem mass spectrometry. This combination was important as the internal standard compensated for a number of potential issues arising from the peculiar analytical properties of Meldonium, while HILIC enabled the required chromatographic separation required to accurately determine the
compound’s molecular mass and that of its diagnostic product ions. Overall, an unequivocal identification of
Meldonium was achieved.

You found Mildronate positives in 2.2% of samples studied. Were the results what you expected to find? 
I was surprised to see this prevalence. It was considerably higher than I expected.

What are your thoughts on the PCC Micro-Grant program that was used to fund the Mildronate study? 
In my opinion, the PCC Micro-Grant program is extremely valuable. To render doping controls effectively and timely, anti-doping research requires not only conventional funding programs (which are undisputedly of great importance) but also a tool that allows reacting faster and enables the
rapid production of information vital for handling imminent issues.

Which anti-doping projects will you be pursuing next? 
Quite a few activities are planned, such as expanding doping control sampling options (e.g. by utilizing alternative
matrices such as dried blood spots), and improving test methods to enhance the
coverage of both established doping agents and emerging drugs.

What would you consider your proudest scientific accomplishment? 
I would not have a definite answer to this question. There have been a few situations wherein we were told doping
analysis related problems could not be solved using analytical chemistry.
However, eventually we were able to prove quite the opposite.

Why should a young scientist consider the field of anti-doping research? 
It is an enormously dynamic field of research. Many questions raised in this arena are related to other disciplines
(e.g. toxicology, forensics, clinical chemistry, etc.), but necessitate a different angle and approach to provide the
information relevant to sports drug testing. The enormous interdisciplinary aspect offers great opportunities for
scientific exchange and cooperation; probably more pronounced than in most other fields of applied research.
Dr. Thevis is a Professor for Preventive Doping Research and Vice President of Research at the German
Sport University Cologne’s Institute of Biochemistry / Center for Preventive Doping Research. 

His research on Mildronate can be found at http://onlinelibrary.wiley.com/enhanced/doi/10.1002/dta.1788