Novel substances of expected doping activity are constantly introduced to the market. β-Methylphenethylamine (BMPEA) is classified as a doping agent by the World Anti-Doping Agency as it is a positional isomer of amphetamine. In this work, the development and application of a simple and rapid analytical procedure that enables discrimination between both isomers is described. The analytes of interest were extracted from urine by a two-step liquid–liquid extraction and then analyzed by UPLC/MS/MS under isocratic conditions. The entire analytical procedure was validated by evaluating its selectivity, discrimination capabilities, carry-over, sensitivity, and influence of matrix effects on its performance. Application of the method resulted in detection of BMPEA in eight anti-doping samples, including the first report of adverse analytical finding regarding its use. Further analysis showed that BMPEA may be eliminated unchanged along with its phase II conjugates, the hydrolysis of which may considerably improve detection capabilities of the method. Omission of the hydrolysis step may therefore, produce false-negative results. Testing laboratories should also carefully examine their LC/MS/MS-based amphetamine and BMPEA findings as both isomers fragment yielding comparable collision-induced dissociation spectra and their insufficient chromatographic separation may result in misidentification. This is of great importance in case of forensic analyses as BMPEA is not controlled by the public law, and its manufacturing, distribution, and use are legal.

Higenamine (Norcoclaurine) is a very popular substance in Chinese medicine and is present in many plants. The substance may be also found in supplements or nutrients, consumption of which may result in violation of anti-doping rules. Higenamine is prohibited in sport at all times and included in Class S3 (β-2-agonists) of the World Anti-Doping Agency (WADA) 2017 Prohibited List. The presence of higenamine in urine samples at concentrations greater than or equal to 10 ng/mL constitutes an adverse analytical finding (AAF). This work presents a new metabolite of higenamine in urine sample which was identified by means of ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were prepared according to 2 protocols - a Dilute and Shoot (DaS) approach and a method involving acid hydrolysis and double liquid-liquid extraction (LLE). To meet the requirements typical for a confirmatory analysis, the screening procedure was further developed. In samples prepared by the DaS method, 2 peaks were observed; the earlier one was specific for higenamine and the later one unknown. MS scan analysis showed mass about 80 Da higher than that of higenamine. In turn, in samples prepared in accordance with the protocol involving hydrolysis, an increase in the area under peak for higenamine was observed, while the second peak was absent. It seems that the described strategy of detection of higenamine in urine avoids false negative results.

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Fibromuscular dysplasia (FMD), regarded as a generalized vascular disease, may affect all vascular beds and may result in arterial stenosis, occlusion, aneurysm, or dissection. It has been proposed to systematically evaluate all vascular beds in patients with FMD, regardless of initial FMD involvement. However, the impact of this approach on clinical decisions and on management is unknown. Within the prospective ARCADIA-POL study (Assessment of Renal and Cervical Artery Dysplasia–Poland), we evaluated 232 patients with FMD lesions confirmed in at least one vascular bed, out of 343 patients included in the registry. All patients underwent a detailed clinical evaluation including computed tomography angiography of intracranial and cervical arteries, as well as computed tomography angiography of the abdominal aorta, its branches, and upper and lower extremity arteries. In the study group, FMD lesions were most frequently found in renal arteries (87.5%). FMD was also found in cerebrovascular (24.6%), mesenteric (13.8%), and upper (3.0%) and lower extremity (9.9 %) arteries. Newly diagnosed FMD lesions were found in 34.1% of the patients, and previously undetected vascular complications were found in 25% of the patients. Among all FMD patients included in the study, one out of every 4 evaluated patients qualified for interventional treatment due to newly diagnosed FMD lesions or vascular complications. The ARCADIA-POL study shows for the first time that the systematic and multidisciplinary evaluation of patients with FMD based on a whole-body computed tomography angiography scan has an impact on their clinical management. This proved the necessity of the systematic evaluation of all vascular beds in patients with FMD, regardless of initial FMD involvement.

2-(Ethylthio) benzimidazole is an active ingredient of Antihot, a dietary supplement sold in Ukraine. The substance, available also under names of Bemitil, Metaprot, and Bemaktor, was developed in the USSR in 1970s, and after tests on Soviet cosmonauts and soldiers, several studies on its influence on athletes' performances were conducted. The research showed that bemitil is a synthetic adaptogen which is capable to significantly increase physical performance and reduce the time of regeneration.Moreover, according to supplement's distributor, the substance improves both physical performance and resistance to stress. Taking into account these properties, it appears plausible that the World Anti-Doping Agency (WADA) decided to include bemitil in its 2018 monitoring program. To select markers of bemitil use, six doses of the supplement (two per day, on three consecutive days) were administrated to six healthy volunteers (three men, three women, 26-49 years). Urine samples were collected before, during and up to 30 days after the first ingestion. Samples were analyzed by means of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The study revealed that bemitil can be traced in urine as either a parent compound or its glucuronide conjugate, which is more abundant and has a wider detection window. KEYWORDS 2-ethylsulfanyl-1H-benzimidazole (WADA), 2-(Ethylthio)benzimidazol (ANTIHOT), anti-doping analysis, Bemitil, excretion study

Selective androgen receptor modulators were developed as a treatment of choice for diseases that are currently treated or symtomatically treated with steroidal androgens. The present study aimed to explore the metabolic pathways of four structurally unrelated SARMs, namely, PF‐06260414, TFM‐4AS‐1, BMS‐564929, and GSK 2881078, in terms of their potential toxicology or doping control analysis. Detected metabolism, mainly resulting from a single or multiple hydroxylations, methoxylation, demethylation, dehydrogenation, and glucuronidation, was considered as potential markers of intake of examined SARMs.

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