Dietary supplement for energy and reduced appetite containing the β-agonist isopropyloctopamine leads to heart problems and hospitalisations

Abstract

In 2013 the Dutch authorities issued a warning against a dietary supplement that was linked to 11 reported adverse reactions, including heart problems and in one case even a cardiac arrest. In the UK a 20-year-old woman, said to have overdosed on this supplement, died. Since according to the label the product was a herbal mixture, initial LC-MS/MS analysis focused on the detection of plant toxins. Yohimbe alkaloids, which are not allowed to be present in herbal preparations according to Dutch legislation, were found at relatively high levels (400-900 mg kg). However, their presence did not explain the adverse health effects reported. Based on these effects the supplement was screened for the presence of a β-agonist, using three different biosensor assays, i.e. the validated competitive radioligand β2-adrenergic receptor binding assay, a validated β-agonists ELISA and a newly developed multiplex microsphere (bead)-based β-agonist assay with imaging detection (MAGPIX®). The high responses obtained in these three biosensors suggested strongly the presence of a β-agonist. Inspection of the label indicated the presence of N-isopropyloctopamine. A pure standard of this compound was bought and shown to have a strong activity in the three biosensor assays. Analysis by LC-full-scan high-resolution MS confirmed the presence of this 'unknown known' β3-agonist N-isopropyloctopamine, reported to lead to heart problems at high doses. A confirmatory quantitative analysis revealed that one dose of the preparation resulted in an intake of 40-60 mg, which is within the therapeutic range of this compound. The case shows the strength of combining bioassays with chemical analytical techniques for identification of illegal pharmacologically active substances in food supplements. ARTICLE HISTORY

Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC–MS/MS

“…This product was found to contain synephrine, methylsynephrine, isopropyloctopamine, and caffeine along with other components 40 . A study published later found 40–60 mg isopropyloctopamine per dose in the three batches of the suspect supplement analyzed 41 . In this study, the presence of phenylephrine or etilefrine was not detected in any of the analyzed products.…”

Getting More Than You Paid For: Unauthorized “Natural” Substances in Herbal Food Supplements on EU Market

“…Examples of UHPLC-QTOF-MS applications include quantification of yohimbine, synephrine, and oxilofrine [35,84,103,104], while QqQ was mostly used for analysis of synephrine and octopamine [105][106][107][108]. Orbitrap, on the other hand, was used for analysis of yohimbine [104,109], arecoline [110], and isopropyloctopamine [93]. LC with UV detection, either in form of a single-wavelength detection or PDA, was also used in several applications.…”

“…In the UK, a 20-year-old woman, said to have overdosed on this supplement, died. The levels of natural phenylethanolamines, although relatively high, could not explain the incidence of side effects, but the presence of isopropyloctopamine led to suspicion that isopropyloctop-amine was the compound responsible for most of the observed side effects [93]. A supplement containing synephrine, octopamine, tyramine, and caffeine caused coronary spasm and thrombosis in a bodybuilder [78], while a series of adverse effects caused by a supplement containing multiple active ingredients, including isopropyloctopamine, was described before [35].…”

Revision of the National Residue Control Plan - application on the red meat supply chain

“…The use of effect-based screening has the advantage that, alongside the standard substances, new unknown substances and designer drugs can be detected (Van Ginkel & Sterk, 2016). They are also deployed for forensic research in areas beyond the scope of the NP (Bovee et al, 2016).…”