Detection of clostebol in sports: accidental doping?

Code: 20C15XD

Clostebol (4-chloro-testosterone; 4-chloro-4-androsten-17-ol-3-one) is an anabolic androgenic steroid (AAS) derivative from testosterone. In humans, among the legitimate therapeutic indications of anabolic steroids, clostebol acetate is approved for topical use in dermatological and ophthalmological preparations. The esterification on the 17 position also permits its oral use, protecting the compound from an extensive firstpass metabolism. Clostebol has also been used in cattle to improve the animal growth. Due to its anabolic properties the International Olympic Committee (IOC) in the past and today the World Antidoping Agency (WADA) have included clostebol and the other AAS in the yearly renewed list of prohibited substances in sports[1]. The human [2,3] and animal[4] metabolism of clostebol allowed to establish adequate methods to 
detect its illicit use. The detection of clostebol intake is traditionally based on the detection of its main metabolite (4-chloro-4-androsten-3a-ol-17-one) excreted into urine glucuronoconjugated (Figure 1.). In order to improve the detection capabilities, antidoping laboratories have developed in the last decade methods based on gas chromatography (GC) coupled to tandem mass spectrometry (MS/MS) lowering the limits of detections or have implemented methods for the direct investigation of phase II metabolites (sulphates) using liquid chromatography coupled to mass spectrometry (LC-MS/MS) [5,6]. The presence of clostebol metabolite in an athlete’s urine sample may be due to its illicit use as anabolic, the ingestion of contaminated meat[7] and finally some case reports describe the accidental contact with cream preparations containing clostebol[8]
. 
In the last years, the improvement of the detection capabilities of the antidoping laboratories has led to a moderate increase of clostebol detection worldwide, and especially in Italy where the use of a cream containing clostebol acetate and neomicine is quite extended. Trofodermin® is a pharmaceutical preparation containing 5% clostebol acetate and 5% neomicine sulphate that can be applied by cream or spray, that can be used for the following treatments: abrasions and erosions of the skin, injuries and wounds, such as varicose ulcers, due to poor blood circulation, bedsores (due to immobility in bed) sores or trauma, fissures (cuts) on the nipple (which can occur during breastfeeding), anal fissures (small cuts around the anus), burn wounds, infected wounds, wounds that delay to form the scar, irritation, redness, and sensitization of the skin that appears after radiotherapy (radiodermatitis), dryness, cracking or peeling of the skin with ulceration. According to the Italian law, a visible symbol on the packaging indicating the presence of a substance included in the WADA list of prohibited substances must be present. Although clostebol is prohibited by all administration routes, the aim of this study is to investigate the presence of clostebol metabolite in urine after an accidental contact with the substance due to the therapeutic application of clostebol acetate in a different individual.