Detection of sibutramine in herbal food supplements by UHPLC/HRMS and UHPLC/MS-MS. Elina Petkova-Gueorguieva 1 , Kalin Ivanov 2 , Stanislav Gueorguiev 1 , Anna Mihaylova 3* , Vasil Madzharov 1 , Stanislava Ivanova 2 1 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria 2 Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria 3 Medical University of Plovdiv, Medical College, Plovdiv, Vasil Aprilov Blvd. 15-A, Bulgaria Abstract Recent studies have announced that many food supplements for weight loss contained undeclared sibutramine. We have analysed 10 samples of herbal weight loss food supplements (FS) by HPLC/HRMS and UHPLC/MS-MS. We have established that two of the analysed samples contained sibutramine: respectively 5 µg/per capsule and 20 µg/per capsule. Illegal inclusion of this substance in FS could cause serious side effects and long term health consequences. The regulatory requirements for FS should be enhanced for more comprehensive consumers’ protection. The need for mandatory quality control of these products and public awareness is undeniable. Keywords: Sibutramine, HPLC, Food supplements, Analysis, Undeclared substances, WADA. Accepted on July 17, 2018 Introduction Sibutramine or 1-(1-(4-chlorophenyl) cyclobutyl)-N, N, 3- trimethylbutan-1-amine (Figure 1) is a serotonin-noradrenaline re-uptake inhibitor which was used as a weight loss drug in the recent past [1]. It was approved as an anti-obesity drug in 1997 by FDA and in 1999 by the European Medicines Agency (EMA). It has been established that sibutramine intake increased risk of heart attacks and strokes [2,3]. Since 2010, when EMA concluded that the benefits of sibutramine as weight loss drug do not outweigh its risks, sibutramine drugs have been suspended throughout Europe [1]. Drugs containing sibutramine were withdrawn voluntarily by the manufacturer from the U.S. market in 2010 [2]. Sibutramine has been withdrawn also from the pharmaceutical market of many other countries like: Australia, New Zealand, Canada, China, India, Mexico and others [4-6]. Nowadays there are many cases of undeclared sibutramine in herbal food supplements (FS) for weight loss [7-18]. A variety of techniques could be used successfully for detection of sibutramine: HPLC/MS, HPLC- ESI-MS, LC-MS/MS and HPTLC. Illegal inclusion of this substance in FS could cause serious health consequences for consumers like non-fatal myocardial infarction and nonfatal stroke [3]. Sibutramine intake is also associated with numerous side effects: agitation; problems with vision, speech, or balance; dry mouth; upset stomach; flu symptoms, insomnia, skin rash and others. Figure 1. Sibutramine. Material and Methods Materials Reference standard: Sibutramine hydrochloride monohydrate with purity>98%. Reagents: Acetonitrile for HPLC, (Sigma Aldrich), distilled water. Samples: 10 herbal food supplements for weight-loss. Samples were purchased from dietary supplement stores, pharmacies and online. ISSN 0970-938X www.biomedres.info Biomed Res 2018 Volume 29 Issue 14 3006 Biomedical Research 2018; 29 (14): 3006-3009