Detection of the diuretic hydrochlorothiazide in a doping control urine sample as the result of a non-steroidal anti-inflammatory drug (NSAID) tablet contamination

Diuretic agents are prohibited in sports in- and out-of-competition according to the regulations of the World Anti-Doping Agency (WADA) because of their possible masking effects on other doping agents in urine samples, and their ability to produce fast acute weight losses. Despite previous studies reported adverse analytical findings (AAFs) resulting from contaminations at ppm level (μg/g) of medicinal products, and recommended to introduce reporting limits for diuretics in doping controls, these are not adopted in analyses performed by WADA-accredited laboratories. We report the case of an athlete with two AAFs for hydrochlorothiazide (HCTZ) at low urinary concentrations (<10 ng/mL), who declared the use of nutritional supplements prepared in a compounding pharmacy. His nutritional supplements were analyzed revealing HCTZ presence in different concentrations, at the ppm level (μg/g and ng/mL). With the aim of testing the plausibility of the observed urinary HCTZ concentrations with the nutritional supplement ingestion, a urinary excretion study with three healthy volunteers was performed. HCTZ-contaminated powder (6.4 μg/g of HCTZ) was administered to each subject in different dosages, reproducing the possible ingestion pattern occurred. Urine specimens were collected before and after ingestion of the powder, up to 24 hours, and underwent liquid-liquid extraction and liquid chromatography-tandem mass spectrometry determination. Post-administration specimens were found to contain HCTZ at concentrations of 5-230 ng/mL, which supported the accidental inadvertent intake of the prohibited substance by the athlete. This study makes the argument that the introduction of reporting limits for diuretics are warranted in doping control samples, in order to protect against inadvertent AAFs due to contaminated products.

Section: Hctz Excretion Studiesmentioning

confidence: 98%

Section: Reporting Limits Of Non-threshold Substancesmentioning

confidence: 99%

mentioning

confidence: 99%

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Multiple incidence of the prescription diuretic hydrochlorothiazide in compounded nutritional supplements

Favretto

Visentin

Scrivano

et al. 2018

“…The risk of inadvertent ingestion of prohibited substances through contaminated food, water, supplements and medications is a growing problem, particularly if considering the increase of the instrument sensitivity and of the analytical performance in anti‐doping laboratories …”

Section: Introductionmentioning

confidence: 99%

Hair analysis to discriminate voluntary doping vs inadvertent ingestion of the aromatase inhibitor letrozole

Favretto

Snenghi

Pértile

et al. 2018

Letrozole is an aromatase inhibitor, used to treat postmenopausal women with hormone receptor‐positive or unknown advanced breast cancer. It is prohibited in sport because it is used together with androgen anabolizing steroids to avoid their adverse effects. In the case of an adverse analytical finding, it may be important to distinguish between repetitive use due to voluntary administration and occasional use, possibly due to involuntary intake. With the objective to identify the dose capable of producing a positive hair test, and to apply these results to the scenarios of inadvertent letrozole ingestion by an athlete, this study investigates the urinary excretion and incorporation into hair of single doses of letrozole. Seven subjects were recruited for an excretion study of letrozole and its metabolite bis(4‐cyanophenyl) methanol (M1) in urine, after the consumption of 0.62 mg, 1.25 mg, and 2.5 mg of letrozole, and to investigate the incorporation in hair after ingestion of 0.62 mg and 2.5 mg of letrozole. Urine and hair samples were also obtained from two women in chronic therapy. Urinary concentrations of letrozole and its metabolite M1 were lower in subjects administered once with 0.62 mg, 1.25 mg, or 2.5 mg letrozole than in women in regular therapy with 2.5 mg/day. In hair collected after a single dosage, concentrations of 16–60 pg/mg were detected while in women in chronic therapy concentrations were higher than 160 pg/mg all along the hair shaft. Hair analysis turned to be a promising possibility for the discrimination of letrozole repetitive use vs occasional/inadvertent administration.

“…The world of sport has been confronted with a substantial number of anti‐doping rule violations and associated scandals in the past 12 months. This situation was epitomized by the alleged existence of government‐supported doping programs (similar to those of the former German Democratic Republic) but also by cases of unusual pharmacokinetics of the recently prohibited drug meldonium and the inadvertent administration of doping agents . The gravitas of such cases is fuelling debate for an overhaul of the global anti‐doping system .…”

Section: Introductionmentioning

confidence: 99%

Annual banned‐substance review: analytical approaches in human sports drug testing

Thevis

Kuuranne

Geyer

et al. 2017

Self Cite

There has been an immense amount of visibility of doping issues on the international stage over the past 12 months with the complexity of doping controls reiterated on various occasions. Hence, analytical test methods continuously being updated, expanded, and improved to provide specific, sensitive, and comprehensive test results in line with the World Anti-Doping Agency's (WADA) 2016 Prohibited List represent one of several critical cornerstones of doping controls. This enterprise necessitates expediting the (combined) exploitation of newly generated information on novel and/or superior target analytes for sports drug testing assays, drug elimination profiles, alternative test matrices, and recent advances in instrumental developments. This paper is a continuation of the series of annual banned-substance reviews appraising the literature published between October 2015 and September 2016 concerning human sports drug testing in the context of WADA's 2016 Prohibited List. Copyright © 2016 John Wiley & Sons, Ltd.