NIST’s Reference Material Supports Anti-Doping Efforts in International Sports

Illustration shows a winner's wreath suspended over a vial labeled IGF-1.
NIST has produced a standard reference material that can be used to support testing for performance-enhancing drugs.
Credit:

B. Hayes/NIST

This summer has been exciting for sports enthusiasts: Many athletic events are back in full swing, and the Olympic Games are finally taking place after being delayed a full year by the pandemic. Despite this pause, modern sporting events have rules and regulations that reflect years of change. Today’s athletes are prohibited from using performance-enhancing drugs and are required to pass drug tests to be able to compete in the Olympics and many other events.

But how do we know that the methods used to test athletes for drugs are accurate and equivalent between methods over time? The National Institute of Standards and Technology (NIST) has created a standard reference material (SRM) to help anti-doping laboratories ensure that their testing methods give accurate results: NIST SRM 2926 (Recombinant Human Insulin-like Growth Factor 1).

NIST’s reference material is already being used by the World Anti-Doping Agency (WADA) and the U.S. Anti-Doping Agency (USADA) and has been available for more than a year. However, this year’s Olympics is the first in which the SRM will be used. In addition to its sporting applications, the reference material could also improve medical care, by potentially helping to ensure accurate tests for patients experiencing imbalances in growth hormones because of pituitary gland disorders.

In sports, the word “doping” means the use of banned substances by athletes to improve their performance. In 2018, a total of 263,519 samples taken from athletes were analyzed by WADA-accredited laboratories, and of those, 1,640 were confirmed to show evidence of anti-doping rule violations (ADRV). Among the sports with the most ADRVs were bodybuilding and cycling.

Even though the total number of violations is small compared with the number of samples tested, it shows that performance-enhancing drugs are still used by many athletes. Athletes can abuse a wide variety of banned substances, and NIST’s efforts will help detect one in particular: artificially injected human growth hormone (hGH).

Athletes use hGH as a performance-enhancing drug because of effects that can improve their athletic performance, such as reducing body fat, increasing muscle mass and strength, and repairing tissue in the musculoskeletal system. However, the drug also produces many negative side effects, such as worsening of cardiovascular diseases; muscle, joint and bone pain; hypertension; and heart failure.

Testing athletes for illegal drugs is pretty straightforward. The key steps include selecting and notifying athletes for testing, collecting and analyzing samples, and reporting the results. To help make tests for human growth hormone as accurate as possible, NIST researchers developed an SRM containing insulin-like growth factor 1 (IGF-1).

“IGF-1 is a small human protein. When an athlete injects growth hormone, there is an increase in IGF-1. So, to catch these athletes, laboratories measure levels of both the human growth hormone and IGF-1,” said NIST researcher David Bunk.

NIST’s reference material consists of three vials of a frozen solution of protein in a buffered aqueous solution. The SRM is stored in a freezer at minus 62.2 degrees Celsius (minus 80 degrees Fahrenheit) and shipped to customers in dry ice to keep the material frozen until used.

Containing precisely known levels of IGF-1, the material can be used to calibrate lab measurements of IGF-1 in human blood samples. For the doping testing process this material could play a critical role during the sample analysis stage to ensure accurate measurements.

“IGF-1 is a small human protein. When an athlete injects growth hormone, there is an increase in IGF-1. So, to catch these athletes, laboratories measure levels of both the human growth hormone and IGF-1.” -David Bunk, NIST researcher

Within the U.S., there were no standardized reference materials for IGF-1 that anti-doping laboratories could use; the new SRM has filled that need. “SRM 2926 is likely to be used to calibrate test methods used for measurement of IGF-1 in human blood samples,” said Bunk. “To compare measurement results from different methods, the best approach is to measure a common sample using the different methods. If the methods are calibrated differently, it’s unlikely that they will give equivalent measurement results. Having a common calibration, such as one prepared by SRM 2926, provides a level playing field for method comparison.”

International WADA-accredited laboratories have their own reference materials for IGF-1 and other doping agents. The NIST SRM now serves as a calibrator for their anti-doping testing for IGF-1.

“WADA regularly works with national measurement institutes around the world to develop certified reference materials that support the fight against doping in sports,” said Olivier Rabin, WADA’s senior executive director of sciences and international partnerships. “WADA is grateful to NIST for the development and distribution of a reference material for the analysis of IGF-1, which is now routinely used in anti-doping laboratories.”

The anti-doping applications for the SRM are likely to be wide-ranging, including for major sporting events from the World Cup in soccer to the Grand Slam tournaments in tennis.

SRM 2926 applications, though, go beyond just the athletic fields. It also can be used to calibrate measurements of IGF-1 in clinical settings for patients who have an imbalance in their hGH production. These imbalances can be caused by a disruption of the pituitary gland, which produces hGH and can affect IGF-1 concentration levels. In this case, IGF-1 is used as a bioindicator to see if the hGH concentration is too low or too high.

NIST has also produced a companion reference material called SRM 2927, 15N-Labeled Recombinant Human Insulin-like Growth Factor 1. This SRM contains the same IGF-1 protein but is designed to be used exclusively in anti-doping laboratories to enable them to perform internal checks on their own measurements. SRM 2927 is used as an internal standard, while SRM 2926 calibrates the methods.

“When making measurements, it’s good to have a sample that provides an accurate baseline. You want the measurement to be the same across all samples. SRM 2927, in its use as an internal standard, acts as the North Star for these measurements,” said Bunk.

Both SRM 2926 and 2927 are available from NIST, and organizations wishing to purchase the SRMs can visit the NIST SRM webpage.

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