Detection of Undeclared Halogen Substituted Drug Compound in a Natural Health Product

Abstract

INTRODUCTION:The U-Dream line of products are marketed as natural health product sleep aids in Canada and as dietary supplements in the United States. Several user reviews of the product mention concerning side effects not typically associated with the listed herbal ingredients stated on the product label. Based on these concerns an analytical study was undertaken to determine if the products contained any undeclared pharmaceuticals. METHODS:Product was screened by high resolution mass spectrometry (HRMS) for known pharmaceuticals with sedative and sleep promoting properties. Based on the mass spectral screens an unknown compound was isolated for characterization by nuclear magnetic resonance (NMR) and presence confirmed by Enzymelinked Immunosorbent Assay (ELISA). RESULTS:The mass spectral analyses indicated the presence of an undeclared analogue of the pharmaceutical drug zopiclone within the product lot tested. NMR characterization confirmed the compound to be a brominated analogue of zopiclone and a commercial zopiclone/eszopiclone ELISA kit tested positive. DISCUSSION: The undeclared compound was found to be an analogue of zopiclone whereby the chlorine atom was substituted with bromine. Given the results of the ELISA assay and the structural similarity to zopiclone it is likely the compound exhibits biological activity. Of considerable concern is not only the potential of the unknown compound to exhibit pharmacological activity, but the lack of a safety profile by which the risk can be properly assessed. CONCLUSIONS:The natural health product regulations provide a framework for high quality, safe and efficacious products to access the market. It is the responsibility of the manufacturer to assure traceability and transparency in their supply chain and establish verifiable compliance with GMP. This study illustrates the importance of careful evaluation of analytical data in order to detect undeclared adulterants and highlights the need for an active monitoring and surveillance system for potentially high-risk products.

Adulteration of Brain Health (Cognitive, Mood, and Sleep Enhancement) Food Supplements by the Addition of Pharmaceutical Drugs: A Comprehensive Review of Analytical Approaches and Trends

“…The potential of elucidating compounds’ structures is pivotal in the identification of drug analogues and has allowed the detection of new substances added in PFS with activity at the brain level. The work of Brown et al [ 15 ] is a very good example of such capabilities. In 2020, the authors examined products of the U-Dream line, marketed as a natural health product for sleep aids in Canada and as dietary supplements in the U.S., following diverse reports of side effects by numerous consumers.…”

“… Full-scan mass spectrum of peak eluting at 3.9 min in the HR-LCMS Orbitrap analysis of the U-Dream product. Reprinted from [ 15 ] under the terms of the Creative Commons Attribution License. …”

“…Food supplements adulterated with APIs are a major public health problem since they may seriously affect the health of consumers, with several cases of adverse effects, hospitalizations, and even deaths being reported [ 13 , 14 ]. Moreover, the presence of slightly modified molecules (API analogues) to circumvent their detection by the authorities has also been detected in these products, which further increases the associated risk since for most of these compounds, no studies exist about their safety, toxicity, and efficacy [ 15 , 16 ].…”