Positive doping results caused by the single-dose local injection of triamcinolone acetonide

Abstract

Triamcinolone acetonide (TA) is classified as an S9 glucocorticoid in the 2014 Prohibited List published by the World Anti-Doping Agency, which caused it to be prohibited in-competition when administered orally, intravenously, intramuscularly or rectally. The Minimum Required Performance Level (MRPL) for the detection and identification of glucocorticoids is 30 ng/mL. Other common local injection routes, such as intraarticular, intratendinous, or intrabursal injection, are not prohibited. The purpose of this study was to analyze the TA and triamcinolone (T) concentrations in urine after a single injection of TA in patients to determine if it would produce a positive result. This study was performed on 40 patients with sports injuries or joint pains. TA was administered locally (doses varied from 12 to 80 mg). Samples were extracted using a solid-phase extraction column, followed by hydrolysis and liquid extraction using diethyl ether. The elution solvents were collected and dried. The dried residue was reconstituted and assayed by performing liquid chromatography-tandem mass spectrometry (LC-MS/MS) in positive ionization mode using electrospray ionization and multiple-reaction monitoring as the acquisition mode. The results demonstrated that the concentrations of both TA and T in urine exceeded the MRPL (30 ng/mL) after a single local injection. We obtained positive results for TA in 25 patients, and a positive result for T in one patient. Furthermore, the metabolic situation of TA, a long-acting glucocorticoid, was not an exact linear model. The highest concentrations of TA and T appeared 1-4h after injection. This information could be useful for limiting the misuse of TA by athletes. We suggest that athletes be aware when using TA injections during a competition period and obtain approval for therapeutic use exemption prior to using TA.

Elimination profile of triamcinolone in urine following oral administration

“…The amount of T excreted in urine was much lower after the intra‐tendinous injection of the acetonide form compared to that excreted after the oral administration, even though the urinary T concentrations might be greater than the MRPL of 30 ng/mL (urinary T concentrations of the 2 volunteers was published by Chang et al).…”

“…Urinary T concentrations were determined by a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method described by Chang et al A 4‐mL aliquot of urine, KH 2 PO 4 buffer, and betamethasone‐D5 (internal standard) were mixed. Solid‐phase extractions (SPEs) were performed by doubly deionized water, acetic acid, and methanol progressively.…”

“…We also calculated the urinary pharmacokinetic parameters of T and TA after intra‐tendinous injections of TA) The t 1/2 of T and TA were 1.4 ± 0.9 hours and 31.5 ± 17.4 hours, respectively. The t 1/2 of T was much shorter than t 1/2 of T. TA was released slowly in the duration due to the character of suspension dosage form, but there were no T were detected 4 hours after injected.…”

“…However, previous studies have indicated that the general reporting level of 30 ng/mL may not be suitable for all glucocorticoids and their metabolites due to wide therapeutic doses, different administration routes, and different elimination conditions . Although T is a minor metabolite of TA, urine concentrations of T might exceed the MRPL after a legal local injection of TA . Hence, it is crucial to distinguish the administration route and/or the form of the drug and recognize how long a drug remains in the body when a prohibited substance is detected.…”

“…Although oral T form is also a common form among diverse T derivatives, most studies have focused on the pharmacokinetics of triamcinolone acetonide (TA) after administration via different routes (ie, oral, intravenous, intramuscular, and inhalation) . Only a few studies have investigated the pharmacokinetics of T administered orally.…”