Department of Pharmacology and Toxicology, Raymond Poincaré Hospital, GHU AP-HP.Paris-Saclay, 92380 Garches, France; Paris-Saclay University, UVSQ, Inserm U-1018, CESP, Team MOODS, Plateform MasSpecLab, 78180 Montigny-le-Bretonneux, France.
Department of Pharmacology and Toxicology, Raymond Poincaré Hospital, GHU AP-HP.Paris-Saclay, 92380 Garches, France.
Clin Chim Acta. 2025 Jan 15;565:120002. doi: 10.1016/j.cca.2024.120002. Epub 2024 Oct 12.
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.
奥克托品，也称为二甲己胺（DMHA），是一种中枢神经系统兴奋剂。当人类摄入奥克托品时，它会迅速代谢为庚胺醇，这是血液中主要存在的化合物。由于其兴奋剂活性，奥克托品及其代谢物被世界反兴奋剂机构（WADA）禁用清单 S6b 部分“特定兴奋剂”指定为禁用物质，禁止在比赛中使用。但在某些情况下，它们可能因污染而导致不良分析结果（AAF），尿液中浓度较低。在这种情况下，毛发测试可以根据测量的浓度或目标药物的不存在来区分兴奋剂与污染。然而，文献中没有可用的数据。本研究的目的是开发一种用于定量检测头发中奥克托品和庚胺醇的液相色谱-串联质谱（LC-MS/MS）方法，并将其应用于一名尿液中庚胺醇（尿液样本 A 和 B 经比重校正后分别为 141 和 136 ng/mL）和奥克托品（16 ng/mL，WADA 实验室未在样本 A 中检出，低于 50 ng/mL 的最低请求水平）存在 AAF 的运动员。分析了运动员服用的所有补充剂，并在 AAF 后两个月采集了阴毛（黑色，1.5-2 厘米长，没有头发生长）和脚趾甲屑（0.1 厘米）。一种补充剂被确定为污染来源，其中含有浓度在 16-34μg/g 之间的奥克托品。运动员在 AAF 前 20 天每天服用 13 克（0.2-0.4 毫克奥克托品），总剂量为 4-8 毫克。他的阴毛和脚趾甲屑中只含有庚胺醇（分别为 30 pg/mg 和 3 pg/mg）。对一名志愿者进行了一项对照研究，该志愿者服用了一次 13 克受污染的补充剂（奥克托品的单次剂量为 0.2-0.4 毫克）。他的尿液中同时含有这两种化合物，其浓度与 AAF 当天运动员的浓度非常接近，摄入和采样之间的时间间隔约为 4 小时。一个月后，他的头发生长和阴毛分别只含有 2 和 3 pg/mg 的庚胺醇，脚趾甲屑中两种化合物均为阴性。WADA 委员会接受了污染，但运动员仍因在互联网上购买补充剂而被禁赛 9 个月。
