A research team led by Mississippi State University’s Dr. Amanda Patrick recently completed a PCC-funded project on beta-2 agonists, revealing new fundamentals of how the prohibited substances behave in a mass spectrometry environment. These findings could lay the groundwork for better detection, including the ability to differentiate between therapeutic use and athlete abuse.

Beta-2 agonists are one of the substance classes prohibited at all times by WADA. However, they are also commonly used to treat asthma and other respiratory ailments.  Because therapeutic use of these drugs, especially salbutamol, is widespread, there are a number of exceptions built into the rules. For several of these agonists, there are accepted detection limits rather than the substances being banned outright.

Salbutamol is administered therapeutically as a racemic mixture. That means it contains a 50-50 balance of an active version of the substance, called a “eutomer”, and an inactive, mirror image of the same substance. Currently, common tests only look at total content, so if an athlete took a dose that was solely made up of the eutomer without any of the inactive match, a “double dose” could be taken without surpassing the threshold for detection.

The aim of this pilot project was to evaluate several potential paths toward differentiation of the racemic mixture from the pure eutomer using mass spectrometry (an analytical chemistry instrument that “weighs” molecules and their fragments) and related instruments. To this end, the researchers gained many new fundamental insights into how beta-2 agonists behave in the environment of the mass spectrometer.

The first publication from this work describes the gas-phase dissociation pathways of four beta-2 agonists, including salbutamol, in the mass spectrometer. Understanding this behavior could be key to future advances in detecting abuse of beta-2 agonists.

Dr. Patrick adds of the work, “Analytical advances are often built on improved understanding of the underlying chemistry involved and our team is very excited to have the chance to help build such a fundamental understanding of how beta-2 agonists behave in the mass spectrometry environment toward anti-doping goals.”

The team has also begun development of a method for differentiating racemic versus eutomer-spiked urine through the generation and dissociation of specific metal complexes with the compounds being studied. The further evaluation, development, and refinement of this method will be the subject of future work.