A burst of fenoterol excretion during the recovery of a weight loss protocol.

Fenoterol is a sympathomimetic ß2 receptor agonist primarily used as a bronchodilator. Due to its sympathomimetic actions, the World Anti-Doping Agency (WADA) has banned it. Multiple acute weight loss protocols (WLP) are used by Olympic athletes for sports that segregate athletes by weight; these generally involve caloric and water deprivation combined with heat exposure. Athletes use WLP before weigh-in, then transition to different body acute weight regain protocols (WRP) before competitions. Here, we studied the pharmacokinetics of fenoterol under WLP conditions: energetic dietary restriction, decreased water intake, and exposure to a dry sauna (80 ± 2 °C), followed by a WRP. Five elite-level female judo athletes participated in the study. Four received fenoterol (200 µg; n = 2 or 400 µg; n = 2), while one was a control receiving placebo under identical conditions. We measured excretion of the fenoterol parent molecule and presented qualitative data of its sulfated metabolite using QqQ tandem quadrupole mass spectrometry for 118 h. The fenoterol parent appeared earlier in urine than did its conjugated metabolite; excretion profiles were similar among all subjects. The centers of mass for fenoterol parent curves were (time, fenoterol): athlete A (10.9, 7.3); athlete B (9.2, 27.3); athlete C (8.5, 6.9); athlete D (9.7, 5.0). After initiating WRP, we observed a burst in urinary fenoterol excretion once in complete decay. This trend was observed for all four athletes who received fenoterol. Our results suggest that during hypohydration, some of the unmetabolized fenoterol accumulates in tissues, then is released during rehydration. These findings can be important for detecting fenoterol use in athletes.

Dietary higenamine from Annonaceae family fruits as a possible source of unintentional doping.

Members of the genus Aconitum have been used for millennia, both as poisons and medicines, in Eastern culture. Higenamine has non-selective beta-agonist effects, activating both ß1 and ß2 adrenoreceptors, and is present in a variety of plants. The World Anti-Doping Agency has banned Higenamine both in competition and out of competition. Due to the common uses of higenamine in Brazilian culture, both as medicine and food, we studied the urinary concentrations of higenamine after the consumption of fruits of the Annona genus. We evaluated whether the ingestion of these fruits has the potential to cause anti-doping code violations. We measured higenamine concentrations for a 72 h period in the urine of ten healthy, physically active males (age 20-30; weight 70-80 kg; not consuming supplements or medications) after eating a unique meal containing fruits. Fruit consumption ranges were: Carica papaya (control) 348 ± 98 g; A. muricata 450 ± 282 g; and A. squamosa 314 ± 60 g. (all mean± SD). Higenamine was measured using ultra-performance liquid chromatography coupled with electrospray-tandem mass spectrometry. The appearance of urinary higenamine occurred within the first 12 h after eating A. muricata (n = 3), and the maximum concentration found was 1.9 ng/mL. The ingestion of A. squamosa has also been shown to cause higenamine urinary excretion. The elimination kinetics of the subjects who ingested A. squamosa (n = 4) were different from each other. After ingestion of the control fruit, C. papaya, we detected no higenamine in the urine of any participants (n = 3). Although the kinetics varied by individuals and fruits, A. muricata ingestion produced higher higenamine excretion; however, the A. squamosa portion weighed ∼66 % of the A. muricata portion. We conclude that eating Annonaceae family fruits cause detectable higenamine excretion. Conversely, single ingestion did not reach the WADA's threshold to cause adverse analytical findings.