Criteria for establishing illicit use of synthetic glucocorticoids.
According to WADA regulations, glucocorticoids may be used in sports when applied locally (inhalation, intradermal and intraarticular application) but other means of delivery are prohibited (oral or anal introduction, intravenous or intramuscular injection). The main objective of this study was to determine the limits of positivity as a function of the corticoid used and its type of administration. This is important in helping determine urinary concentrations and times required for corticoid elimination.
It was also possible to measure two other parameters as a function of the corticoid used and its type of administration: the ratio of the free corticoid fraction to that of the eliminated conjugated forms and the evolution of the endogenous profile. Intraindividual and interindividual variations were given special attention throughout the work.
Corticosteroids have been used in sports medicine for many years to treat tendinopathies, ligamentary lesions, and various overuse syndromes. They are also used in asthma management. However there is no consensus about the efficiency of such treatments and good recommendations are rare. There is often little knowledge about the correct dosage and the right methods of injections and comparison with other therapeutic approaches is often lacking. Prior to this work, when exogenous corticosteroids were indeed detected, it was not possible to determine the mode of administration or even estimate the time when the drug was first administered. The mere presence of corticosteroids in the urine did not tell whether it was applied locally, orally ingested, inhaled or injected.
The inability to determine the mode of administration of a substance should not lead to any relaxation in its prescription. It should, to the contrary, incite the experts to better define applicability and to develop corresponding good therapeutic practices. In practice, unrestricted corticoid use simply could not be authorized and the World Anti-Doping Agency (WADA) rapidly enacted clear rules regulating these substances. In December 2004, WADA set the threshold of positivity at 30 ng/ml, but this value had no real scientific basis.
This study was initiated and funded by WADA to remedy the lack of pharmacological evidence in this domain and to clearly define the limits of positivity as a function of the corticosteroid used and its mode of administration. The study, lasting two years (2006 et 2007), was carried out in collaboration with the Paris and the Sydney laboratories
A total of 66 volunteers participated in this study according to the plan on the right.
1164 urinary samples were collected and analyzed in the laboratory using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The results are summarized in the table on the right.
- It is possible to differentiate cutaneous corticosteroid administration and inhalations (nasal or pulmonary) from the other modes of administration. A limit of positivity can be established for each individual corticoid.
- In contrast, it is not possible to differentiate intraarticular injections from systemic administration. WADA must therefore evaluate and reclassify this mode of administration.
- The ratio of the free fraction to the conjugated form depends on the corticoid used, its mode of administration and individual metabolism. The conjugated fraction is often significant.
- Systemic administration of corticoids leads to a collapse in the endogenous profile. This is particularly true for endogenous cortisone and cortisol which is almost completely absent in the urine,
- The study confirmed the importance of intraindividual and interindividual variability which must be taken into account when evaluating collected data.
- Avois L, Bailloux I, Desmarcheliers A, Lahaussois A, Méchin N, Saugy M, de Ceaurriz J.
Synthetic glucocorticosteroids administration: urinary excretion study of triamcinolone acetonide. 25nd Cologne Workshop on Dope Analysis, 26 Février - 2 Mars 2007, Cologne (Allemagne)
- Bailloux I, Avois L, Desmarcheliers A, Lahaussois A, Méchin N, Gremion G, Saugy M, de Ceaurriz J. Elimination of seven synthetic glucocorticosteroids in urine according to the route of administration: preliminary results. 26nd Cologne Workshop on Dope Analysis, 24-29 Février 2008, Cologne (Allemagne)
- Avois L, Bailloux I, Desmarcheliers A, Lahaussois A, Méchin N, Saugy M, de Ceaurriz J. Synthetic glucocorticoids administration: urinary excretion of triamcinolone acetonide.
Recent Advances in Doping Analyses 15, in: Proceedings of the Manfred Donike Workshop. 25th Cologne Workshop on Dope Analysis,419-423