Evaluation of the reporting level to detect triamcinolone acetonide misuse in sports

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Triamcinolone hexacetonide (THA) is a synthetic glucocorticoid (GC) used by intra‐articular (IA) administration. GCs are prohibited in sports competitions by systemic routes, and they are allowed by other routes considered of local action (IA administration, among others). The aim of the present work was to study the metabolic profile of THA in urine and plasma following IA administration. Eight patients (4 males and 4 females) with knee osteoarthritis received an IA dose of THA (40 mg) in the knee joint. Spot urine and plasma samples were collected before injection and at different time periods up to day 23 and 10 post‐administration, respectively. The samples were analysed by liquid chromatography‐tandem mass spectrometry. Neither THA nor specific THA metabolites were detected in urine. Triamcinolone acetonide (TA) and 6β‐hydroxy‐triamcinolone acetonide were the main urinary metabolites. Maximum concentrations wereobtained between 24 and 48 h after administration. Using the reporting level of 30 ng/mL to distinguish allowed from forbidden administrations of GCs, a large number of false adverse analytical findings would be reported up to day 4. On the other hand, TA was detected in all plasma samples collected up to day 10 after administration. THA was also detected in plasma but at lower concentrations. The detection of plasma THA would be an unequivocal proof to demonstrate IA use of THA. A reversible decrease was observed in plasma concentrations of cortisol in some of the patients, indicating a systemic effect of the drug.

Section: Introductionmentioning

confidence: 99%

Elimination profile of triamcinolone hexacetonide and its metabolites in human urine and plasma after a single intra‐articular administration

Coll

Matabosch

Llorente‐Onaindia

et al. 2019

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“…In addition, T is not a major metabolite of TA in humans . Hence, lower recovery obtained after intra‐tendinous injections of TA compared to oral administration of T. Previous study also indicated that the very low excreted rate of T after IM injection of TA …”

Section: Discussionmentioning

confidence: 99%

“…It is noteworthy that intra‐tendinous injection is a common and permitted administration route of TA . Apart from different metabolic conditions among individuals, previous studies indicated that part of the T detected in urine samples might come from the impurities in pharmaceutical preparation . Either way, it may cause a false‐positive result which is detrimental to athletes’ achievement.…”

Section: Discussionmentioning

confidence: 99%

“…An atypical finding or adverse analytical finding should be reported once the urine level exceeds the MRPL . 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 .…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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Elimination profile of triamcinolone in urine following oral administration

Chen

Tseng²,

Huang

et al. 2017

Triamcinolone (T) is a glucocorticoid commonly used to relieve inflammation and treat arthritis, severe allergies, and asthma; however, it is banned by the World Anti-Doping Agency in competition for athletes when administered orally, intravenously, intramuscularly, or rectally. The minimum required performance limit (MRPL) for urinary T is 30 ng/mL. However, the data about the urinary excretion of T after oral administration is limited. We investigate the elimination profile and determine whether single-dose administration of T would cause a positive doping result. Twelve healthy volunteers received a single-dose of 4-mg T rally, and urine samples were collected for 24 hours. A validated liquid chromatography-tandem mass spectrometry method was used to determine urinary T levels. Non-compartmental modeling was used to estimate the pharmacokinetic parameters. All the urinary T concentrations were much higher than the MRPL. The peak urinary T concentration was 3211.4 ± 860.3 ng/mL (mean ± SD), time to peak concentration was 1.7 ± 0.9 hours, and the estimated elimination half-life was 4.4 ± 2.8 hours. About 27.76% of the consumed dose was eliminated via urine within 24 hours of intake. After a single-dose oral administration, urinary T concentrations still exceeded the MRPL after 24 hours. This information could be useful for limiting the misuse of T. Athletes should be aware when using T in competition and acquire approval for a therapeutic use exemption prior to use. Moreover, the elimination profile of orally administered T may be crucial information for distinguishing different dosage routes.

Detection and characterization of betamethasone metabolites in human urine by LC‐MS/MS

Matabosch

Pozo

Monfort

et al. 2014

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Glucocorticosteroids are prohibited in sports when administered by systemic routes and allowed using other administrations for therapeutic reasons. Therefore, markers to distinguish between routes of administration through the analysis of urine samples are needed in anti-doping control. As a first step to achieve that goal, the metabolism of betamethasone (BET) was investigated in the present work. Urine samples obtained after BET intramuscular injection were hydrolyzed with β-glucuronidase and subjected to liquid-liquid extraction with ethyl acetate in alkaline conditions. The extracts were analyzed by liquid chromatography coupled to tandem mass spectrometry. Common open screening methods for fluorine containing corticosteroids (precursor ion scan method of m/z 121, 147, 171, and neutral loss (NL) scan methods of 20 and 38 Da in positive ionization, and 46 and 76 Da in negative ionization) were applied to detect BET metabolites. Moreover, an NL method was applied to detect A-ring reduced metabolites of BET, which are ionized as [M+NH4 ](+) (NL of 55, 73, and 91 Da, corresponding to the consecutive losses of NH3 , HF and one, two and three water molecules, respectively). BET and 24 metabolites were detected. Six metabolites were identified by comparison with standards, and for ten, feasible structures were proposed based on mass spectrometric data. Eleven of the characterized metabolites had not been previously reported. Metabolites resulting from 11-oxidation, 6-hydroxylation, C20 or 4-ene-3-one reduction and combination of some of them were detected. Moreover one metabolite resulting from cleavage of the side chain with subsequent oxidation of carbon at C17 was also detected.