Discrimination between zeranol and zearalenone exposure using hair analysis. Application to an adverse analytical finding case

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.

Section: Discussionmentioning

confidence: 99%

“…[29][30][31][32] Cases of AAFs for prohibited substances detected in urine, where hair analysis was performed to provide complementary information and judge the origin of the positive finding, include Clostebol, 33 diuretics, 34 steroids 35,36 and non-steroidal estrogens. 37…”

Section: Case Reportmentioning

confidence: 99%

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

Favretto

Snenghi

Pértile

et al. 2018

“…This is possible with hair tests and has been used to demonstrate no significant fault or negligence. 33 In theory, this should also be used to discriminate the prohibited S4 metabolic modulator trimetazidine from the metabolic conversion of the permitted drug lomerizine, a drug used for the treatment of migraines. Testing human hair for clenbuterol, a ß-adrenergic agonist with anabolic properties allows discriminating therapeutic use from contamination, based on the measured concentrations.…”

Section: Introductionmentioning

confidence: 99%

“…Another application‐based on parent drug detection is the discrimination between zeranol, a S1 banned substance and zearalenone, a mycotoxin, which share the same metabolite(s). This is possible with hair tests and has been used to demonstrate no significant fault or negligence . In theory, this should also be used to discriminate the prohibited S4 metabolic modulator trimetazidine from the metabolic conversion of the permitted drug lomerizine, a drug used for the treatment of migraines.…”

Section: Introductionmentioning

confidence: 99%

Hair testing for doping agents. What is known and what remains to do

Kintz¹,

Gheddar

Ameline

et al. 2020

Self Cite

Hair testing is a complementary approach to document doping agent(s) use All prohibited substances but hormones should be detectable in hair Interest and limitations of hair testing for doping agents are reviewed based on the authors' experience Although a lot of data are available for drugs of abuse, controlled studies are missing for anabolic steroids, diuretics and some unusual classes of substances

“…Although hair testing is not suitable to overrule a positive urine finding, it can significantly contribute to the exculpation of innocent athletes by demonstrating alternative administration pathways or contamination risks . Recently, this role of hair testing was demonstrated in a case where hair analysis allowed the discrimination between the mycotoxin zearalenone and its urinary metabolite zeranol, which is banned for its anabolic properties . In the present study, we developed an ultra‐high performance liquid chromatography –tandem mass spectrometry (UHPLC–MS/MS) method to detect clostebol and clostebol acetate in hair and applied this method to three real cases of athletes sanctioned for clostebol use, in order to follow up investigations of doping control laboratories and obtain useful elements to understand the origin of these positive findings, and two forensic cases in which some anabolic drugs abuse was to be assessed.…”

Section: Introductionmentioning

confidence: 99%

Hair analysis can provide additional information in doping and forensic cases involving clostebol

Salomone

Gerace

Corcia

et al. 2018

Self Cite

Clostebol is a synthetic anabolic androgenic steroid, with potential use as a performance-enhancing drug if taken for long periods in order to produce the desired effect. Recently, the use of medications containing clostebol acetate has led to the suspension of several athletes in various sports. Previous studies have shown that urine can result positive in case of single intake of a banned substance, including unintentional consumption of steroids. In this context, a hair test can contribute to exculpation of athletes by demonstrating alternative administration or contamination. The development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to detect clostebol and clostebol acetate in hair is hereby presented. Some real cases of athletes sanctioned for clostebol use, in which we analyzed hair samples to follow up investigations of doping control laboratories and obtain useful elements to understand the origin of clostebol intakes, and two forensic cases of anabolic drugs abuse, are also presented and discussed. In real head- and body-hair samples, clostebol acetate could be detected in the low pg/mg range. As is typical of hair analysis, the interpretation of the quantitative findings may be challenging, and even more in sports owing to the lack of systematic studies. However, the results can be used to produce evidence contrary to any ruling issued against the athletes by the appropriate sports body, and possibly obtain a diminished sanction. Because the sports authorities do not make a distinction among circumstances or means of administration of anabolic compounds, athletes should be warned not to use clostebol-containing medications.