Content area
Full Text
Higenamine (HG), 6,7,12-trihydroxy-benzyl-1,2,3,4-tetrahydroisoquinoline, is an alkaloid isolated from several plants belonging to the genera Nandina, Aconitum, Asarum, Galium, Annona, and Lotus [1,2]. HG was first separated from aconite root by Kosuge and Yokota in 1976 [3] and has received attention from healthcare professionals for its cardioactive properties since then. HG can stimulate β-adrenergic receptors [4,5] and exert inotropic and chronotropic effects on the cardiovascular system through anti-platelet aggregation, inhibition of iNOS, and upregulation of HO-1 expression [6–10]. HG has also been used in a cardiac stress test in the treatment of acute diseases, including disseminated intravascular coagulation, heart failure, ischemia/reperfusion injury, and spinal cord injury [11,12].
Since HG is a β2-receptor agonist, the International Olympic Committee (IOC) has prohibited its use by athletes [13]. In January 2017, the World Anti-Doping Agency (WADA) included HG in the prohibited list of S3 group (β2-receptor agonists) [14]. Reports in the literatures indicate that HG is widely distributed in plants and even in some food materials and medicines, such as weight loss products, energy drinks, or additives for sports function products [15,16], leading to the potential risk of consumption of HG by athletes. Therefore, athletes must be prevented from eating HG-containing vegetable drugs or food materials in advance. However, judging whether an athlete takes foods, medicines, or illegal drugs containing HG requires urine or blood tests. Therefore, it is important to establish a sensitive and reliable HG detection method suitable for various matrixes. According to the list of HG-containing drugs, nutrients and food products, and the test requirements of biological samples issued by the China Food and Drug Administration [17], different matrixes have been classified (Table 1).
Because the listing of HG in the doping category is issued recently, there are relatively few analytical methods to detect HG at present. The most commonly used detection methods are high performance liquid chromatography (HPLC) [18], capillary electrophoresis (CE) [19], and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) [11,13,20–22]. Although derivatization methods are used in the HG detection...