Doping Control Using High and Ultra-High Resolution Mass Spectrometry Based Non-Targeted Metabolomics-A Case Study of Salbutamol and Budesonide Abuse

Abstract

We have detected differences in metabolite levels between doped athletes, clean athletes, and volunteers (non athletes). This outcome is obtained by comparing results of measurements from two analytical platforms: UHPLC-QTOF/MS and FT-ICR/MS. Twenty-seven urine samples tested positive for glucocorticoids or beta-2-agonists and twenty samples coming from volunteers and clean athletes were analyzed with the two different mass spectrometry approaches using both positive and negative electrospray ionization modes. Urine is a highly complex matrix containing thousands of metabolites having different chemical properties and a high dynamic range. We used multivariate analysis techniques to unravel this huge data set. Thus, the several groups we created were studied by Principal Components Analysis (PCA) and Partial Least Square regression (PLS-DA and OPLS) in the search of discriminating m/z values. The selected variables were annotated and placed on pathway by using MassTRIX.

β‐2 Agonists as Misusing Drugs? Assessment of both Clenbuterol‐ and Salbutamol‐related European Medicines Agency Pharmacovigilance Database Reports

“…This is the most likely reason of the four cases of fatal overdosage ADRs, not being associated with abuse or dependence, here identified in underage subjects. Overall, overdosage and off-label use issues were identified slightly more frequently in salbutamol (typically in association with remaining medications), as opposed to clenbuterol, cases (respective salbutamol versus clenbuterol PRR values: 1.32 and 1.33), with this being consistent with previous findings [30,[47][48][49][50].…”

Ion traps in modern mass spectrometry

“…Another life science field recently addressed with FT‐ICR is sports doping analysis, targeting metabolites of various dopants.…”

Combining UHPLC and high-resolution MS: A viable approach for the analysis of complex samples?

“…There were also successful approaches to detecting biomarkers of banned compounds (e.g., salbutamol and budesonide) when the pharmaceutically-active drug had been completely excreted [63].…”