Applications of Higenamine in pharmacology and medicine

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.

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

“…Higenamine stimulates beta‐adrenergic receptors (β‐AR)and is considered as an effective anti‐obesity agent . Higenamine is very popular in Chinese medicine and there are numerous papers devoted to its use …”

Section: Introductionmentioning

confidence: 99%

“…It is expected that the substance is actually a racemic mixture of 2 enantiomers: (S)‐(‐)‐higenamine and (R)‐(+)‐higenamine.Its chloride salt is commonly used for clinical purposes mainly because it is relatively more soluble in water than other salts. Higenamine hydrochloride is a very stable compound occurring in the form of an intensively white powder …”

Section: Introductionmentioning

confidence: 99%

Analysis for higenamine in urine by means of ultra‐high‐performance liquid chromatography–tandem mass spectrometry: Interpretation of results

Grucza

Kwiatkowska

Kowalczyk

et al. 2017

Higenamine (Norcoclaurine) is a very popular substance in Chinese medicine and is present in many plants. The substance may be also found in supplements or nutrients, consumption of which may result in violation of anti-doping rules. Higenamine is prohibited in sport at all times and included in Class S3 (β-2-agonists) of the World Anti-Doping Agency (WADA) 2017 Prohibited List. The presence of higenamine in urine samples at concentrations greater than or equal to 10 ng/mL constitutes an adverse analytical finding (AAF). This work presents a new metabolite of higenamine in urine sample which was identified by means of ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were prepared according to 2 protocols - a Dilute and Shoot (DaS) approach and a method involving acid hydrolysis and double liquid-liquid extraction (LLE). To meet the requirements typical for a confirmatory analysis, the screening procedure was further developed. In samples prepared by the DaS method, 2 peaks were observed; the earlier one was specific for higenamine and the later one unknown. MS scan analysis showed mass about 80 Da higher than that of higenamine. In turn, in samples prepared in accordance with the protocol involving hydrolysis, an increase in the area under peak for higenamine was observed, while the second peak was absent. It seems that the described strategy of detection of higenamine in urine avoids false negative results.

“…Higenamine (1‐[(4‐hydroxyphenyl)methyl]‐1,2,3,4‐tetrahydroisoquinoline‐6,7‐diol) is a non‐selective β2‐agonist, which is present in various natural plants, e.g. Aconitum , Nelumbo nucifera , Tinospora crispa , Nandina domestica , and Gnetum parvifolium …”

Section: Introductionmentioning

confidence: 99%

“…By contrast, higenamine is a key component of traditional Chinese herbal medicine . The Nandina domestica , Thunberg, has been commonly used as a cough medicine in Japan for decades, and the component most responsible for the medicinal effects of Nandina domestica has been identified to be higenamine …”

Section: Introductionmentioning

confidence: 99%

Determination of higenamine and coclaurine levels in human urine after the administration of a throat lozenge containing Nandina domestica fruit

Okano¹,

Sato²,

Kageyama³

2017

Higenamine is a key component of traditional Chinese herbal medicine. The fruit of Nandina domestica (which contains this component) is available as an ingredient in the so-called Nanten-nodo-ame throat lozenge found on the Japanese market, which is an over-the-counter pharmaceutical and is easy to purchase for Japanese athletes. However, higenamine is a nonselective β2-agonist, which is exemplified in the prohibited list of the World Anti-Doping Agency (WADA). Therefore, some have raised a concern regarding the potential cause of increased unintentional higenamine doping cases in the Asian region. This study aimed to investigate components of throat lozenges and develop a mass-spectrometry method for the quantification of higenamine and coclaurine in human urine. Moreover, a population study of Japanese subjects (n = 246) and an excretion study (n = 4) of the corresponding throat-lozenge recipients were performed to test the applicability of the current reporting threshold (i.e., 10 ng/mL) of higenamine set by WADA. The estimates of higenamine and coclaurine were 2.2 ± 0.1 μg/drop (mean of n = 12) and 0.5 ± 0.01 μg/drop (mean of n = 12), respectively. The maximum concentrations of higenamine and coclaurine were 0.2-0.4 and 0.3-1.0 ng/mL, respectively, at 10-12 h after administration of higenamine (nine drops); however, the concentrations in all four volunteers did not reach the positivity criterion of 10 ng/mL. No higenamine and coclaurine could be detected in the Japanese subjects. Therefore, there is no risk of detecting unintentional higenamine doping when the WADA reporting threshold is used.