Identification and Quantification Methodology for the Analysis of Suspected Illegal Dietary Supplements: Reference Standard or no Reference Standard, that the Question

The consumption of food supplements has become a billion dollar business that has proliferated across the globe. Consequently this also resulted in the increase of adulterations by the illegal addition of medicinal substances or their analogues. The vast majority of the pharmaceutical substances encountered in those samples belong to the three ‘classical’ categories, including sexual enhancers (e.g. PDE-5 inhibitors and flibanserine), weight loss enhancers occasionally accompanied with an anti-depressant (e.g. sibutramine, phenolphthalein, sibutramine and fluoxetine or venlafaxine) and sports performance enhancers (e.g. selective androgen receptors (SARMs) and anabolic-androgenic steroids (AAS)). Recently also chemicals belonging to the class of pharmaceutical cognition enhancers or nootropics are gaining popularity amongst the general public. While for many of the classical categories reference standards are available to unambiguously confirm the identity of a pharmaceutical product, for several molecules, including some nootropics, no certified reference material is available. Hereby, with the example of an adrafinil containing food supplements, we show how, by utilising multiple methodologies, we were able to come to identification and subsequent quantification when no certified reference standard was available. Furthermore, in 2017 already several food supplements analysed by our lab were positive for the presence of nootropic substances, indicating that these compounds are really gaining popularity amongst the general public.