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

Abstract

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.

Do dried blood spots (DBS) have the potential to support result management processes in routine sports drug testing?

“…A considerable number of studies into urinary glucocorticoid eliminations following the administration of different drug formulations and varying routes of administration has been conducted, supporting today's result interpretation in case of AAFs related to glucocorticoids as necessitated by the permitted use of glucocorticoids during out‐of‐competition periods as well as via routes that are not considered to result in systemic effects and effective blood concentrations 31–36 . To date, AAFs concerning glucocorticoids are issued when a glucocorticoid is detected at concentrations exceeding the reporting level of 30 ng/mL, 3 thus largely disregarding the potencies and correspondingly required therapeutic dosages of glucocorticoids.…”

Annual banned‐substance review: Analytical approaches in human sports drug testing 2019/2020

“…Similarly, the metabolic transformation and elimination of triamcinolone acetonide (TA) as well as triamcinolone hexacetonide (THA) was studied, with TA being administered either intranasally (220 μg/day for 3 days) or intramuscularly (single dose, 40 mg), 165 and THA intraarticularly (single dose, 40 mg) 166 . Urinary TA concentrations remained below 3.5 ng/ml upon intranasal administrations, while the main metabolite 6β‐hydroxytriamcinolone increased to 93 ng/ml.…”

“…Urinary TA concentrations remained below 3.5 ng/ml upon intranasal administrations, while the main metabolite 6β‐hydroxytriamcinolone increased to 93 ng/ml. Conversely, the intramuscular drug administration resulted in urinary TA concentrations up to 129 ng/ml; hence, a reporting level of 5 ng/ml was suggested to support the distinction between the permitted and prohibited use of the glucocorticoid 166 . Investigations into the elimination of the legitimate use of intraarticular THA applications however demonstrated that urinary TA was determined at levels exceeding 30 ng/ml for up to 4 days.…”

“…Aiming at supporting the differentiation of legitimate from illegitimate use of corticoids in sport, a series of elimination studies was conducted with various glucocorticoids including budesonide, triamcinolone (hex)acetonide, prednisone, and prednisolone, and time-aligned urinary concentrations of respective markers were determined. Budesonide was administered intranasally (256 μg/ Similarly, the metabolic transformation and elimination of triamcinolone acetonide (TA) as well as triamcinolone hexacetonide (THA) was studied, with TA being administered either intranasally (220 μg/ day for 3 days) or intramuscularly (single dose, 40 mg),165 and THA intraarticularly (single dose, 40 mg) 166. Urinary TA concentrations remained below 3.5 ng/ml upon intranasal administrations, while the main metabolite 6β-hydroxytriamcinolone increased to 93 ng/ml.…”

The 37th Manfred Donike workshop on doping analysis

“…All glucocorticoids are prohibited in‐competition if administered systemically and, consequently, the means to attribute an adverse analytical finding to both in‐competition use and systemic administration are required. Hence, elimination profiles for triamcinolone hexacetonide as well as prednisone and prednisolone were studied, aiming to identify diagnostic drug and/or metabolite patterns or concentrations. Another complicating factor was addressed in the case of prednisone and prednisolone, which occasionally originate from in situ microbial transformations of naturally occurring endogenous steroids.…”