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

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EarlyView Article

  • Published: Sep 15, 2017
  • Author: Masato Okano, Mitsuhiko Sato, Shinji Kageyama
  • Journal: Drug Testing and Analysis

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 non‐selective 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.

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