Isolation and identification of a sibutramine analogue adulterated in slimming dietary supplements

Abstract

A suspected sibutramine analogue was detected in a slimming functional food by an ultra performance liquid chromatography-electrospray ionisation-time of flight mass spectrometry (UPLC-ESI-TOF/MS) method. The ultraviolet (UV) spectrum of this suspected compound showed close similarity to that of sibutramine. The sample was extracted with 70% MeOH and isolated by semi-preparative column chromatography. The structure of this compound was identified by spectroscopic analyses (nuclear magnetic resonance [NMR] technique, mass and tandem mass etc.). The structure of the unknown compound was demonstrated to be [(±)-dimethyl-1-[1-(3,4-dichlorophenyl)cyclobutyl]-N,N,3-trimethylbutan-1-amine (molecular formula C17H25NCl2) and named as chloro-sibutramine. Compared with sibutramine, it has one more chlorine atom than the 3-cholorophenyl group so was switched to 3,4-dichlorophenyl. Until now, chloro-sibutramine was isolated for the first time from the undeclared ingredient included in dietary supplements. Although the safety of chloro-sibutramine is unknown, there is a potential health risk to consumers because of a similar skeleton to sibutramine. For public health, this sibutramine analogue has been included in the inspection list of illegal adulterants in Korea.

Counterfeit formulations: analytical perspective on anorectics

“…Anorectics (or anorexics) refer to medicines or dietary supplements used for weight-loss purposes [23]. Medicines sold over-the-counter and from Internet sources adulterated with anorectics and/or their analogues or metabolites have been reported [24][25][26][27][28][29]. Similarly, phytotherapeutic (i.e., plant-based) formulations that are deemed "natural product" alternative treatment for obesity have been demonstrated to contain non-declared anorectics and adjuvants that boost their efficacy [24,[30][31][32][33][34][35].…”

Development and validation of an ultra‐performance liquid chromatography method for simultaneous analysis of 20 antihistaminics in dietary supplements

“…The use of dietary supplements has increased dramatically in recent years, including products that contain red ginseng, vitamins, minerals, individually authorized products, aloe and omega‐3 (Korea Food and Drug Administration, ). In fact, the annual sales of dietary supplements in the Republic of Korea are now estimated to exceed US$13 billion, roughly 25% greater than in 2010 (Kim et al ., ). As the market for dietary supplements has become more lucrative, some manufacturers have begun to include antihistamines to enhance the remedial effectiveness of their products for rhinitis or allergy.…”

Detection of sibutramine in herbal food supplements by UHPLC/HRMS and UHPLC/MS-MS

“…Sibutramine has been withdrawn also from the pharmaceutical market of many other countries like: Australia, New Zealand, Canada, China, India, Mexico and others [4][5][6]. Nowadays there are many cases of undeclared sibutramine in herbal food supplements (FS) for weight loss [7][8][9][10][11][12][13][14][15][16][17][18]. A variety of techniques could be used successfully for detection of sibutramine: HPLC/MS, HPLC-ESI-MS, LC-MS/MS and HPTLC.…”