Industry News: Interview with Professor Anthony W. Butch of the UCLA Olympic Analytical Laboratory

01 Aug 2012

As part of our exclusive Olympics feature this month we have interviewed Professor Anthony W. Butch, Director of the UCLA Olympic Analytical Laboratory, a WADA accredited lab, in Los Angeles, USA. Learn how anti-doping testing is conducted in the US and how current research and trends are shaping this invaluable work.

Prof. Butch, could you describe the mission and role of your facility?

The mission of the UCLA Olympic Analytical Laboratory is to provide state of the art drug testing in the fight against doping in sports. To accomplish this mission our laboratory uses sound scientific principles and the most advanced technologies to detect the presence of prohibited substances in urine and blood samples. The laboratory is constantly evaluating the scientific literature and attending conferences to stay at the scientific forefront in the fight against doping. The laboratory is also extremely active in research and has several funded projects focused on improving drug detection methods. All of this is used to generate scientifically defendable testing results to combat doping in sports.

The UCLA Olympic Analytical Laboratory was established in 1982 by a grant from the Los Angeles Olympic Organizing Committee and has carried out anti-doping testing for three Olympic Games (Los Angeles 1984, Atlanta 1996, and Salt Lake City 2002) as well as other major sporting events such as the Soccer World Cup. When it comes to drug testing, the UCLA Olympic Analytical Laboratory is by far the largest of the World Anti-Doping Agency (WADA)-accredited laboratories and analyzed more than 41,000 athlete samples in 2011.

Could you outline the services offered and the analytical techniques used?

Similar to other accredited laboratories, the UCLA Olympic Analytical Laboratory is compliant with the World Anti-Doping Code and works diligently to develop methods to test for all compounds on the WADA prohibited list. This of course includes anabolic agents, peptide hormones (such as growth hormone) and growth factors, beta-2 agonists, hormone and metabolic modulators, diuretics and other masking agents, stimulants, narcotics, cannabinoids, glucocorticosteroids, and beta-blockers. We have also recently introduced screening methods for substances that are reported to be used by athletes such as bath salts (mephedrone, MDPV), synthetic cannabinoids, and numerous selective androgen receptor modulators.

The UCLA Olympic Analytical Laboratory also provides consultative and expert testimony services for our clients, client requested supplement/unknown substance analysis in difficult doping cases, and interpretive services for longitudinal testing data. The laboratory senior staff consists of 4 individuals who have more than 80 years of combined experience in the development and validation of anti-doping tests, and in interpretation of test results.

The majority of drug tests performed by our laboratory use gas chromatography mass spectrometry and liquid chromatography tandem mass spectrometry systems for separation and detection. Synthetic testosterone and testosterone precursor use is detected by measuring the 13C/12C ratio of testosterone metabolites by gas chromatography-combustion-isotope ratio mass spectrometry. Several hormones such as growth hormone, human chorionic gonadotropin (hCG) and luteinizing hormone are measured by immunoassay. Lastly, erythropoietins require isoelectric focusing and/or polyacrylamide gel electrophoresis techniques for separation and identification.

As your own research focuses on improving methods to detect doping can you describe any new techniques or protocols that have been introduced as a result of your research?

In order to provide cutting edge technologies in the fight against doping in sports it is important for anti-doping laboratories to have a robust research program focused on developing new technologies to improve testing methods and/or on identifying designer compounds as they emerge on the black market. Previous research efforts by the UCLA Olympic Analytical Laboratory resulted in the identification of norbolethone, a steroid never marketed, in an athlete’s urine. The unknown steroids tetrahydrogestrinone and desoxymethyltestosterone were also detected and characterized by the laboratory and are now included in routine screening methods for anabolic agents.

The UCLA Olympic Analytical Laboratory is currently receiving funding from several organizations. One project is aimed at establishing improved criteria for detecting the use of synthetic testosterone and testosterone precursors based on the carbon-13 content of various testosterone metabolites. We are also developing a reference method to detect various isoforms of hCG based on liquid chromatography tandem mass spectrometry. The results from this project will be used to harmonize testing across laboratories and establish assay-specific cutoff concentrations to detect hCG use.

Of all the equipment and manufacturers available, how do you decide which technologies to employ?

The majority of testing in an anti-doping laboratory is performed using gas chromatography and liquid chromatography separation systems coupled to mass analyzers (either single or tandem mass spectrometers). Different types of mass spectrometers are available (magnetic sector, time-of-flight, ion-trap, etc.) and the choice depends on the application. The price of new instrumentation is also a factor since a liquid chromatography tandem mass spectrometry system can easily cost more than half a million dollars. Our laboratory tends to stick with the same vendor when purchasing new equipment since we are already familiar with their instrumentation and operating systems, which helps reduce the time required for instrument validation and training of staff. Of course, instrumentation with superior analytical sensitivity and throughput is always highly desirable regardless of the manufacturer.

For sports organizations that have not signed up to the World Anti-Doping Code how does the testing process differ to that for WADA controlled sports?

Many of our clients that are not signatories to the WADA Code still request testing for the same classes of compounds on the WADA prohibited list. When it comes to anabolic steroids, our clients always request testing for all compounds on the prohibited list and for substances with similar chemical structure that might appear in supplements. Not all clients request anabolic steroid testing on every sample and some only target specific sports. Other classes of compounds such as stimulants might be included in the testing menu but may not include all substances on the WADA prohibited list. Diuretics are not always included in the testing menu and are sometimes only performed when the urine is extremely dilute, based on a specific gravity reading. Probably the biggest difference for non Code compliant sports organizations is the period of ineligibility for an anti-doping rule violation.

Can you comment on any recent trends in drug-taking you have seen – perhaps any differences between sports?

We have recently observed a number of athletes that tested positive for methylhexaneamine, a prohibited stimulant. Methylhexaneamine is found in products sold as dietary supplements and is sometimes listed as an ingredient. It is sometimes referred to as geranamine and geranium oil - athletes should stay away from supplements labeled in this manner. We have also recently identified samples that were positive for synthetic cannabinoids. Synthetic cannabinoids (K2, spice) are found in some herbal products and incense that are available from the internet and sold in head shops. Synthetic cannabinoids are often used as a substitute for marijuana and are rapidly becoming a public health concern.

The use of specific doping agents differs among sports. For sports requiring strength, anabolic steroids such as stanozolol and testosterone continue to be popular. In endurance sports, erythropoiesis-stimulating agents such as erythropoietin are used. Many argue that human growth hormone is widely used by athletes and that this trend will continue until a test with a longer window of detection becomes available. A better human growth hormone test will arrive soon.

What is your view on the adoption of the athlete biological passport (ABP)?

I am strongly in favor of any testing that uses an athlete’s own longitudinal blood data to determine biological variation in order to detect significant deviations in the measured parameters. This is a more sensitive method for detecting doping violations then simply using population-based cutoffs.
Longitudinal data is also being used to detect changes in endogenous urinary steroid profiles that occur during exogenous steroid use. The UCLA Olympic Analytical Laboratory routinely provides steroid profile data to clients and offers consultative services on follow-up testing for significant deviations from baseline values. Although this service requires collection of multiple samples and more testing, it is an extremely useful tool for detecting testosterone and testosterone precursor use.

What do you see as the main challenges for the King’s College Anti-Doping Science Centre during the 2012 Olympics and Paralympics?

The biggest challenge for any anti-doping laboratory during the Games is providing timely drug testing results. The 2012 Games will be especially challenging since record numbers of urine and blood samples will be collected for doping control purposes this summer. I am extremely confident in Dr. Cowan’s leadership and know that he has assembled an outstanding scientific team that will provide accurate, timely drug testing results. I do not see any weaknesses in the drug testing program and know that it will be a huge success. Athletes beware! If you dope you will get caught!

Finally, do you have any predictions for this summer’s games?

It is impossible for me to predict what is going to happen at the summer games. I would like to believe that no athlete will be tempted to use a prohibited substance since they know they will get caught if they dope. Unfortunately, I know this is not completely true so like everyone else, I will have to wait to see what happens at the 2012 Games.

Anthony W. Butch, Ph.D., is Professor of Pathology and Laboratory Medicine and Director of the UCLA Olympic Analytical Laboratory, Geffen School of Medicine at the University of California, Los Angeles (UCLA). He is also Section Chief for Chemistry and Toxicology at the UCLA Clinical Laboratories.

Prof. Butch earned his B.S. in medical technology from Michigan State University in 1977 and a Ph.D. in immunology from Wayne State University in 1987. He completed post-doctoral training in Clinical Toxicology/Chemistry and Cellular Immunology at Washington University in St. Louis. Prior to joining the UCLA faculty in 1999, Dr. Butch was an Assistant Professor at the University of Arkansas, where he served as Director of Clinical Chemistry and Immunology at the University Medical Center.

Prof. Butch is a diplomat of the American Board of Clinical Chemistry and a fellow of the World Association of Anti-Doping Scientists. He teaches medical students, fellows, residents and graduate students, and has published more than 140 papers, abstracts and book chapters.