The risk of higenamine adverse analytical findings following oral administration of <i>plumula nelumbinis</i> capsules

Yan, Kenneth; Wang, Xinzhai; Wang, Zhanliang; Wang, Yunfei; Luan, Zhaoqian; Xi, Gao; Wang, Ruiqi

doi:10.1002/dta.2701

Cited by 22 publications

(22 citation statements)

References 16 publications

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“…Although pharmacokinetics studies on HG and methods for its detection have been very widely described over the last few years, most of these studies involved intravenous administration of HG. There are no pharmacokinetic data for orally‐administered and externally applied HG in experimental animals or humans, despite oral administration and external application being the major routes used for delivering traditional Chinese herbal medicines.…”

Section: Introductionmentioning

confidence: 99%

A pharmacokinetics study of orally administered higenamine in rats using LC–MS/MS for doping control analysis

Wang

Xiong

Yang

et al. 2020

Drug Testing and Analysis

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According to WADA guidelines, the presence of Higenamine (HG) in urine should not be ≥10 ng/mL. HG is widely found in materials used in Chinese herbal medicines as well as food and additives. This paper is the first method wherein a rat model has been used to evaluate the pharmacokinetics of orally administered HG by LC–MS/MS and would be helpful in doping control analysis. The method was found to be linear over a concentration range of 0.5(lower limit of quantification, LLOQ)–500 ng/mL for plasma and 0.5(LLOQ)–1000 ng/mL for urine. The values for intra‐ and inter‐day accuracy and precision did not deviate by >12.25% for HG in plasma and 5.87% in urine. Extraction recoveries of HG were 70.30–86.71% from plasma and 74.93%–79.29% from urine. HG was stable in plasma and urine after the extraction process and when exposed to different storage conditions. The findings of this study could provide some reference value for the assessment of HG misuse and for the control of intake and external application of HG‐related materials (foods and medicinal herbs). Our key findings are that high levels of external application or oral administration of HG‐rich materials may lead to a positive urine test for HG in athletes.

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Section: Introductionmentioning

confidence: 99%

A pharmacokinetics study of orally administered higenamine in rats using LC–MS/MS for doping control analysis

Wang

Xiong

Yang

et al. 2020

Drug Testing and Analysis

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“…Higenamine, or norcoclaurine, is an alkaloid acting as β 2 -agonist, whose misuse in sports is prohibited at all times [91][92][93]. Due to its natural occurrence in numerous plants such as Annona squamosa, Aconitum carmichaelii, Plumula nelumbinis, and Nelumbo nucifera, it is often found in pre-workout and fat-burner supplements.…”

Section: Other Substancesmentioning

confidence: 99%

“…Due to its natural occurrence in numerous plants such as Annona squamosa, Aconitum carmichaelii, Plumula nelumbinis, and Nelumbo nucifera, it is often found in pre-workout and fat-burner supplements. However, an unclear or missing labeling of the ingredients of such products has caused several cases of assumed inadvertent doping within the last years [91][92][93]. LC-MS analysis of different preparations neither listing higenamine or relevant plant extracts on their label yielded the alkaloid at concentrations of 0.02-14 mg/g.…”

Section: Other Substancesmentioning

confidence: 99%

Dietary Supplement and Food Contaminations and Their Implications for Doping Controls

Walpurgis

Thomas

Geyer

et al. 2020

Foods

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A narrative review with an overall aim of indicating the current state of knowledge and the relevance concerning food and supplement contamination and/or adulteration with doping agents and the respective implications for sports drug testing is presented. The identification of a doping agent (or its metabolite) in sports drug testing samples constitutes a violation of the anti-doping rules defined by the World Anti-Doping Agency. Reasons for such Adverse Analytical Findings (AAFs) include the intentional misuse of performance-enhancing/banned drugs; however, also the scenario of inadvertent administrations of doping agents was proven in the past, caused by, amongst others, the ingestion of contaminated dietary supplements, drugs, or food. Even though controversial positions concerning the effectiveness of dietary supplements in healthy subjects exist, they are frequently used by athletes, anticipating positive effects on health, recovery, and performance. However, most supplement users are unaware of the fact that the administration of such products can be associated with unforeseeable health risks and AAFs in sports. In particular anabolic androgenic steroids (AAS) and stimulants have been frequently found as undeclared ingredients of dietary supplements, either as a result of cross-contaminations due to substandard manufacturing practices and missing quality controls or an intentional admixture to increase the effectiveness of the preparations. Cross-contaminations were also found to affect therapeutic drug preparations. While the sensitivity of assays employed to test pharmaceuticals for impurities is in accordance with good manufacturing practice guidelines allowing to exclude any physiological effects, minute trace amounts of contaminating compounds can still result in positive doping tests. In addition, food was found to be a potential source of unintentional doping, the most prominent example being meat tainted with the anabolic agent clenbuterol. The athletes’ compliance with anti-doping rules is frequently tested by routine doping controls. Different measures including offers of topical information and education of the athletes as well as the maintenance of databases summarizing low- or high-risk supplements are important cornerstones in preventing unintentional anti-doping rule violations. Further, the collection of additional analytical data has been shown to allow for supporting result management processes.

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“…Lotus seeds and their processed by-products are widely consumed over the world for their high concentration of physiologically active substances [36,37]. Yan et al evaluated the AAF risk associated with higenamine after the administration of lotus plumule capsules [38]; they revealed that oral administration of the capsule presented a high risk of an AAF for higenamine. All participants in their study received a specific commercial capsule, and urine specimens were collected once a day.…”

Section: Human Studymentioning

confidence: 99%

Potential Risk of Higenamine Misuse in Sports: Evaluation of Lotus Plumule Extract Products and a Human Study

et al. 2020

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Since 2017, higenamine has been added to the World Anti-Doping Agency (WADA) prohibited list as a β2-agonist prohibited at all times for sportspersons. According to WADA’s report, positive cases of higenamine misuse have been increasing yearly. However, higenamine occurs naturally in the Chinese herb lotus plumule—the green embryo of lotus (Nelumbo nucifera Gaertn) seeds—commercially available as concentrated powder on the Asian market. This study evaluated the major phytochemical components of lotus plumule products using an appropriate extraction method, followed by a human study in which the products were orally administered in multiple doses to investigate the risk of doping violations. Comparing various extraction methods revealed that optimized microwave-assisted extraction exhibited the highest extraction efficiency (extraction time, 26 min; power, 1046 W; and temperature, 120 °C). Subsequently, the alkaloids in lotus plumule products were quantitatively confirmed and compared. Human study participants (n = 6) consumed 0.8 g of lotus plumule (equivalent to 679.6 μg of higenamine) three times daily for three consecutive days. All participants’ urinary higenamine concentrations exceeded the WADA reporting cut-off of 10.0 ng/mL. Accordingly, lotus plumule consumption may engender adverse analytical findings regarding higenamine. Athletes should avoid consuming lotus plumule-containing products during in- and out-of-competition periods.

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The risk of higenamine adverse analytical findings following oral administration of plumula nelumbinis capsules

Cited by 22 publications

References 16 publications

A pharmacokinetics study of orally administered higenamine in rats using LC–MS/MS for doping control analysis

A pharmacokinetics study of orally administered higenamine in rats using LC–MS/MS for doping control analysis

Dietary Supplement and Food Contaminations and Their Implications for Doping Controls

Potential Risk of Higenamine Misuse in Sports: Evaluation of Lotus Plumule Extract Products and a Human Study

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