{"title":"庚胺醇毛发检测凸显出补充剂中的辛辣碱污染,这是兴奋剂不良分析结果的罪魁祸首。","authors":"Jean-Claude Alvarez , Isabelle Etting","doi":"10.1016/j.cca.2024.120002","DOIUrl":null,"url":null,"abstract":"<div><div>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).</div><div>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.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"565 ","pages":"Article 120002"},"PeriodicalIF":3.2000,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Heptaminol hair testing to highlight octodrine contamination in supplements, responsible for a doping adverse analytical finding\",\"authors\":\"Jean-Claude Alvarez , Isabelle Etting\",\"doi\":\"10.1016/j.cca.2024.120002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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).</div><div>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.</div></div>\",\"PeriodicalId\":10205,\"journal\":{\"name\":\"Clinica Chimica Acta\",\"volume\":\"565 \",\"pages\":\"Article 120002\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-10-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinica Chimica Acta\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0009898124022551\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinica Chimica Acta","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0009898124022551","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Heptaminol hair testing to highlight octodrine contamination in supplements, responsible for a doping adverse analytical finding
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.
期刊介绍:
The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells.
The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.