Heptaminol hair testing to highlight octodrine contamination in supplements, responsible for a doping adverse analytical finding

Abstract

Octodrine, also known as dimethylhexylamine (DMHA), is a central nervous stimulant. When ingested by humans, octodrine is rapidly metabolized to heptaminol, the main compound present in the blood. Due to their stimulant activities, octodrine and its metabolite are specified substances in section S6b “specified stimulants” of the World Anti-Doping Agency (WADA) Prohibited List, prohibited in competition. But in some cases, they can be responsible for an adverse analytical finding (AAF) following contamination, with a low concentration in the urine. In such cases, a hair test can distinguish doping from contamination according to the concentration measured, or the absence of the target drug. However, no data are available in the literature. The aim of this study was to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of octodrine and heptaminol in hair, and to apply it to an athlete with an AAF with heptaminol (141 and 136 ng/mL in urine samples A and B after correction for specific gravity) and octodrine (16 ng/mL, not given by the WADA laboratory in sample A as being below the minimum request level of 50 ng/mL).

All the supplements taken by the athlete were analysed, and pubic hair (black, 1.5–2 cm long, no head hair available) and toenail clippings (0.1 cm) were sampled two months after AAF. A supplement was identified as the source of contamination, containing octodrine at a concentration range 16–34 µg/g. The athlete had taken 13 g daily (0.2–0.4 mg octodrine) for 20 days prior to the AAF (total dose 4–8 mg). His pubic hair and toenail clippings contained only heptaminol (30 pg/mg and 3 pg/mg, respectively). A controlled study was carried out on a volunteer who took a single 13 g dose of the contaminated supplement (single dose of octodrine 0.2–0.4 mg). His urine was positive for both compounds, with concentrations very close to those of the athlete on the day of the AAF after the same delay between intake and sampling (around 4 h). One month later, his head hair and pubic hair showed only heptaminol at 2 and 3 pg/mg, respectively, and toenail clippings were totally negative for both compounds. The contamination was accepted by the WADA commission, but the athlete was still banned for 9 months for having consumed supplements purchased on the internet.