The analysis of heroin samples, before use in the protected environment of user centra, could be a supplementary service in the context of harm reduction. Infrared spectroscopy hyphenated with multivariate calibration could be a valuable asset in this context, and therefore 125 heroin samples were collected directly from users and analysed with classical chromatographic techniques. Further, Mid-Infrared spectra were collected for all samples, to be used in Partial Least Squares (PLS) modelling, in order to obtain qualitative and quantitative models based on real live samples. The approach showed that it was possible to identify and quantify heroin in the samples based on the collected spectral data and PLS modelling. These models were able to identify heroin correctly for 96% of the samples of the external test set with precision, specificity and sensitivity values of 100.0, 75.0 and 95.5%, respectively. For regression, a root mean squared error of prediction (RMSEP) of 0.04 was obtained, pointing at good predictive properties. Furthermore, during mass spectrometric screening, 10 different adulterants and impurities were encountered. Using the spectral data to model the presence of each of these resulted in performant models for seven of them. All models showed promising correct-classification rates (between 92 and 96%) and good values for sensitivity, specificity and precision. For codeine and morphine, the models were not satisfactory, probably due to the low concentration of these impurities as a consequence of acetylation. For methacetin, the approach failed.

A new nicotine delivery system in the form of tobacco-free nicotine pouches was introduced in Europe in 2019. These nicotine bags did not fall under the Tobacco Products Directive (TPD) II, which brought forward regulatory requirements for both cigarettes, related products, and e-liquids. As these pouches did not fall under the scope of the TPD, it was up to the member states to decide which action to be taken if any. Some EU member states banned these nicotine pouches, while others put restrictions on the amount of nicotine, warning messages, and presentation and packaging of the product, and some member states did not take any action. Likely as a result of the ban or restrictions, soon after also, tobacco and nicotine-free pouches became available in the European Union (EU). Early 2024, "NoNIC" pouches, claiming to be tobacco- and nicotine-free, became available on the European market. These pouches are promoted online and clearly target a younger population with a youth-appealing package design and enticing flavors. Upon analysis of different samples utilizing gas chromatography coupled to MS (GC-MS), liquid chromatography coupled to high-resolution tandem mass spectrometry (HRAM LC-MS2), and nuclear magnetic resonance spectroscopy (NMR), it was demonstrated that these pouches were indeed devoid of nicotine but contained the synthetic nicotine homolog 6-methyl nicotine (6-MN) and this up to 20 mg per pouch. Nonetheless, a part of a likely unaware/misled young adult subpopulation has easy access to these products, containing a novel molecule for which limited to no clinical effects are known.

The detection and quantification of additives in tobacco products are critical for ensuring consumer safety and compliance with regulatory standards. Traditional analytical techniques, like gas chromatography–mass spectrometry (GC–MS), liquid chromatography–mass spectrometry (LC–MS), and others, although effective, suffer from drawbacks, including complex sample preparation, high costs, lengthy analysis times, and the requirement for skilled operators. This study addresses these challenges by evaluating the efficacy of mid-infrared (MIR) spectroscopy and near-IR (NIR) spectroscopy, coupled with multivariate analysis, as potential solutions for the detection and quantification of additives in tobacco products. So, a representative set of tobacco products was selected and spiked with the targeted additives, namely caffeine, menthol, glycerol, and cocoa. Multivariate analysis of MIR and NIR spectra consisted of principal component analysis (PCA), hierarchical clustering analysis (HCA), partial least squares-discriminant analysis (PLS-DA) and soft independent modeling of class analogy (SIMCA) to classify samples based on targeted additives. Based on the unsupervised techniques (PCA and HCA), a distinction could be made between spiked and non-spiked samples for all four targeted additives based on both MIR and NIR spectral data. During supervised analysis, SIMCA achieved 87–100% classification accuracy for the different additives and for both spectroscopic techniques. PLS-DA models showed classification rates of 80% to 100%, also demonstrating robust performance. Regression studies, using PLS, showed that it is possible to effectively estimate the concentration levels of the targeted molecules. The results also highlight the necessity of optimizing data pretreatment for accurate quantification of the target additives. Overall, NIR spectroscopy combined with SIMCA provided the most accurate and robust classification models for all target molecules, indicating that it is the most effective single technique for this type of analysis. MIR, on the other hand, showed the overall best performance for quantitative estimation.

Dietary supplements containing red yeast rice (RYR), a fermentation product of the fungus Monascus purpureus grown on white rice, remain popular in Europe as proclaimed cholesterol-lowering aids. The cholesterol-lowering effects are due to the occurrence of monacolin K, which is often present as a mixture of monacolin K lactone (MK) and as monacolin K hydroxy acid (MKA). MK is structurally similar to the cholesterol-lowering medicine lovastatin. Recently, due to safety concerns linked to the use of statins, the European Commission prohibited RYR supplements with a maximum serving exceeding 3 mg of total monacolins per day. Moreover, the amount of the mycotoxin citrinin, potentially produced by M. purpureus, was also reduced to 100 µg/kg. Evidently, manufacturers that offer their products on the European market, including the online market, must also be compliant with these limits in order to guarantee the safety of their products. Therefore, thirty-five different RYR supplements, purchased from an EU-bound e-commerce platform or from registered online pharmacies, were screened for their compliance to the European legislation for citrinin content and the amount of total monacolin K. This was conducted by means of a newly developed LC-MS/MS methodology that was validated according to ISO 17025. Moreover, these supplements were also screened for possible adulteration and any contamination by micro-organisms and/or mycotoxins. It was found that at least four of the thirty-five RYR supplements (≈11%) might have reason for concern for the safety of the consumer either due to high total monacolin K concentrations exceeding the European predefined limits for total monacolins or severe bacterial contamination. Moreover, three samples (≈9%) were likely adulterated, and the labeling of six of the seventeen samples (≈35%) originating from an EU-based e-commerce platform was not compliant, as either the mandatory warning was missing or incomplete or the total amount of monacolins was not mentioned.

More and more countries and organisations emphasise the value of harm reduction measures in the context of illicit drug use and abuse. One of these measures is drug checking, a preventive action that can represent a quick win by tailored consultation on the risks of substance use upon analytical screening of a submitted sample. Unlike drop-in centres that operate within a fixed setting, enabling drug checking in a harm reduction context at events requires portable, easy to use analytical approaches, operated by personnel with limited knowledge of analytical chemistry. In this case study, four different approaches were compared for the characterisation of 3,4-methylenedioxymethamphetamine samples and this in the way the approaches would be applied today in an event context. The four approaches are mid-infrared (MIR), near-infrared, and Raman spectroscopy, which are today used in drug checking context in Belgium, as well as an electrochemical sensor approach initially developed in the context of law enforcement at ports. The MIR and the electrochemical approach came out best, with the latter allowing for a direct straightforward analysis of the percentage 3,4-methylenedioxymethamphetamine (as base equivalent) in the samples. However, MIR has the advantage that, in a broader drug checking context, it allows to screen for several molecules and so is able to identify unexpected active components or at least the group to which such components belong. The latter is also an important advantage in the context of the growing emergence of new psychotropic substances.

In 2019, a global viral pandemic, due to the SARS-CoV-2 virus, broke out. Soon after, the search for a vaccine and/or antiviral medicine began. One of the candidate antiviral medicines tested was ivermectin. Although several health authorities warned the public against the use of this medicine outside clinical trials, the drug was widely used at the end of 2020 and in 2021. Simultaneously, several reports started to emerge demonstrating serious adverse effects after self-medicating with ivermectin. It stands to reason that the self-administration of substandard or falsified (SF) medicines bearing harmful quality deficiencies have contributed to this phenomenon. In order to have a better view on the nature of these harmful quality deficiencies, SF ivermectin samples, intercepted in large quantities by the Belgian regulatory agencies during the period 2021-2022, were analyzed in our official medicines control laboratory. None of the samples (n = 19) were compliant to the quality criteria applicable to medicinal products. These SF products either suffered from a systematic underdosing of the active pharmaceutical ingredient or were severely contaminated with bacteria, two of which were contaminated with known pathogens that cause gastrointestinal illness upon oral intake. In addition to the direct risks of self-medicating with such a product, the improper usage and dosage of ivermectin medication might also facilitate ivermectin tolerance or resistance in parasites. This may have detrimental consequences on a global scale, certainly as the number of newly developed active pharmaceutical ingredients that can safely be used to combat parasites is rather scarce.

Illicit PDE-5 inhibitors are frequently encountered by regulatory agencies. Self-medicating with substandard and falsified (SF) PDE-5 inhibitors could be dangerous as they are likely taken without any medical supervision and might be of poor quality which could result in adverse reactions. In order to provide an overview of the quality deficiencies present in recently seized illicit PDE-5 samples that may pose health risks, we set out to identify the products’ different chemical and/or biological risks. Our results indicate that 38% of the samples harbored a chemical risk including the significant exceedance of the maximum recommended dosage, a large heterogeneity in API content between the different tablets in the same package or blister and the presence of only 40% of the claimed dosage. Moreover, our results also demonstrate that 16 of the 32 samples were not compliant with the internationally set microbiological quality standards. Startlingly, two samples were severely contaminated with potentially pathogenic bacteria, which could result in a gastrointestinal illness upon oral intake.

Herbal products for smoking containing cannabidiol (CBD) are available as "low-tetrahydrocannabinol cannabis products" in most EU countries. In Belgium, Δ9-tetrahydrocannabinol (THC) content of these products must be less than 0.2% w/w, which is also the limit for agricultural hemp. For agricultural hemp, the official and only valid method for European regulators is gas-chromatography coupled to flame ionization detector (GC-FID). There is no such method, for smoking products. Many of these herbal for smoking products are analyzed as part of their quality control and have certificate of analysis. During surveillance by official labs, discrepancies were seen between the official results and the certificate of analysis. In this study, a GC-FID method based on the European method and an ultra-high-performance liquid chromatography coupled to diode array detection (UHPLC-DAD) method were validated and applied for samples analysis in order to investigate these discrepancies. The GC-FID method shows better results for the validation parameters; notably, it has β-expectation tolerance limits within 10% with a β value of 95% while the validated UHPLC-DAD method has β-expectation tolerance limits within 15% with a β value of 90%. Furthermore, the other parameters evaluated are generally better with the GC-FID method. The statistic t test shows that the difference between both methods was significantly different for total-THC, but not significantly different for the total-CBD. The authors state that, as for agricultural hemp, the GC-FID method is to be preferred for the analysis of THC and CBD in products for smoking.

Drug Testing and AnalysisVolume 15, Issue 2 p. 247-249 LETTER TO THE EDITOR Response to letter to the editor: “Comments on ‘discrepancies between validated GC-FID and UHPLC-DAD methods for the analysis of Δ-9-THC and CBD in dried hemp flowers’” Eric Deconinck, Corresponding Author Eric Deconinck eric.deconinck@sciensano.be orcid.org/0000-0001-6980-6684 Scientific Direction Chemical and Physical Health Risks, Service of Medicines and Health Products, Brussels, Belgium Pharmacognosy, Bioanalysis & Drug Discovery, Faculty of Pharmacy, ULB, Brussels, Belgium Correspondence Eric Deconinck, Scientific Direction Chemical and Physical Health Risks, Service of Medicines and Health Products, Sciensano, J. Wytsmanstraat 14, B-1050 Brussels, Belgium. Email: eric.deconinck@sciensano.beSearch for more papers by this authorMichaël Canfyn, Michaël Canfyn Scientific Direction Chemical and Physical Health Risks, Service of Medicines and Health Products, Brussels, BelgiumSearch for more papers by this authorCéline Duchateau, Céline Duchateau Scientific Direction Chemical and Physical Health Risks, Service of Medicines and Health Products, Brussels, Belgium Pharmacognosy, Bioanalysis & Drug Discovery, Faculty of Pharmacy, ULB, Brussels, BelgiumSearch for more papers by this authorKris De Braekeleer, Kris De Braekeleer orcid.org/0000-0002-3910-2990 Pharmacognosy, Bioanalysis & Drug Discovery, Faculty of Pharmacy, ULB, Brussels, BelgiumSearch for more papers by this author Eric Deconinck, Corresponding Author Eric Deconinck eric.deconinck@sciensano.be orcid.org/0000-0001-6980-6684 Scientific Direction Chemical and Physical Health Risks, Service of Medicines and Health Products, Brussels, Belgium Pharmacognosy, Bioanalysis & Drug Discovery, Faculty of Pharmacy, ULB, Brussels, Belgium Correspondence Eric Deconinck, Scientific Direction Chemical and Physical Health Risks, Service of Medicines and Health Products, Sciensano, J. Wytsmanstraat 14, B-1050 Brussels, Belgium. Email: eric.deconinck@sciensano.beSearch for more papers by this authorMichaël Canfyn, Michaël Canfyn Scientific Direction Chemical and Physical Health Risks, Service of Medicines and Health Products, Brussels, BelgiumSearch for more papers by this authorCéline Duchateau, Céline Duchateau Scientific Direction Chemical and Physical Health Risks, Service of Medicines and Health Products, Brussels, Belgium Pharmacognosy, Bioanalysis & Drug Discovery, Faculty of Pharmacy, ULB, Brussels, BelgiumSearch for more papers by this authorKris De Braekeleer, Kris De Braekeleer orcid.org/0000-0002-3910-2990 Pharmacognosy, Bioanalysis & Drug Discovery, Faculty of Pharmacy, ULB, Brussels, BelgiumSearch for more papers by this author First published: 21 October 2022 https://doi.org/10.1002/dta.3388Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume15, Issue2February 2023Pages 247-249 RelatedInformation

During the past decade, e-cigarettes have become increasingly popular. To guarantee their safe use and to comply with the notification requirements of the EU Tobacco Product Directive, the EU member state regulatory authorities need information about the exact composition of the e-liquids and their emissions. However, one of the challenges encountered during the analysis of e-liquids is the presence of the highly abundant e-liquid matrix components propylene glycol and glycerol. In this study, headspace gas chromatography (HS-GC) analysis is presented as an excellent method for the analysis of high volatile components in e-liquids. For the analysis of semivolatile ingredients, an additional sample preparation step is proposed based on a liquid–liquid extraction (LLE) followed by a freeze-out of the matrix components. The developed method was successfully validated in accordance with the validation requirements of ICH guidelines for the quantification of four flavourings with a potential health concern for e-cigarette users.

Quality control of CBD oils on the Belgium market showed that the CBD content not always corresponds to the label claim. There is a pressing need to develop new analytical methods specifically developed to the assay of such oily samples. Analytical issues are, however, encountered for routine analyses due to the matrix complexity, high cost of cannabinoid standards and low Delta 9-THC concentrations. An oily matrix could cause technical damages to analytical instruments and reduce the lifetime of the chromatographic columns. This paper proposes a procedure combining a sample cleanup by QuEChERS, removing the oily matrix, followed by a validated MRM GC-MS/MS method for the routine analysis of CBD oil samples. Eighteen CBD samples were selected on the Belgium market for analysis. This method allows the quantification of CBD, the legality check for the Delta 9-THC content by a CBN standard and the screening of seven other cannabinoids namely CBN, CBDV, CBT, CBC, Delta 8-THC, THCV and CBG. The method was validated at three concentration levels (0.5-1-2% (w/v)) for CBD and (0.05-0.1-0.2% (w/v)) for CBN. The detection limits for CBT, CBD, CBC, Delta 8-THC, CBN and for the other cannabinoids of interest, were 10 and 14 ng/mL respectively. The accuracy profile values for CBD and CBN showed that the beta-expectation tolerance intervals did not exceed the acceptance limits of +/- 20%, meaning that 90% of future measurements will be included within this error range. (C) 2021 Elsevier B.V. All rights reserved.

INTRODUCTION:Since its introduction, the e-cigarette has become a commonly used consumer product. In this study, we investigate whether regulatory changes had an impact on the quality of refill liquids (e-liquids) available on the Belgian market through analysis of their chemical composition. Hence, the nicotine concentration accuracy was investigated in samples before, during and after the implementation of the revised Tobacco Product Directive (TPD) as an indicator of good manufacturing practices. This is, however, not enough to assure the quality. Therefore, extra criteria were also assessed based on TPD requirements. METHODS:By using in-house validated methods, a total of 246 e-liquids purchased prior (2013-2015), during (2016) and after (2017-2018) the implementation of the TPD revisions, were analyzed for the presence of nicotine, nicotine-related impurities, volatile organic compounds (VOCs), caffeine and taurine, and the flavors diacetyl and acetylpropionyl. RESULTS:Although not all manufacturers managed to produce and label their products accurately, nicotine labeling discrepancies have decreased over time. Moreover, also the number of e-liquids, containing high-risk VOCs (10% in 2016 vs. none of the samples in 2017-2018), caffeine (16% in 2017 vs. 5% in 2018), and diacetyl and acetylpropionyl (50% in 2017 vs. 27% in 2018 of sweet-flavored samples) diminished over time. CONCLUSION:Our results demonstrate that the overall quality of the e-liquids has improved after the implementation of the revised TPD. However, the results also show that periodic quality control might be required to ensure further compliance to the TPD. IMPLICATIONS:This study clearly demonstrates that the implementation of the revised TPD has improved the quality of the e-liquids on the Belgian market. However, there are still e-liquids that are not in agreement with the TPD due to nicotine concentration label discrepancies, presence of e-liquid impurities and controversial flavors diacetyl and acetylpropionyl or the additive caffeine.

Background Few data on motivations for using new psychoactive substances (NPS) are available. However, the cost, the legal status, and their accessibility through channels like internet contributed to the popularity of NPS. The objective of this article are first to gain a deeper understanding of the culture surrounding NPS in Belgium and second to define the awareness of the users concerning the content of the NPS they are consuming. Methods Snowball sampling and partners in the drug demand reduction field were used as a gateway in order to reach a heterogeneous study population. In total, 45 users were recruited and in-depth interviews were conducted. The personal experiences of NPS users and their needs for support along the continuum of care were explored through an interview guideline, while subjects were given the opportunity to deposit a NPS sample for forensic analysis in a recognized laboratory. Results A diversity of profiles was found among NPS users but also a wide diversity in the motives to consume NPS: personal reasons such as pleasure, mind exploration, being connected to others, or out of curiosity, but also external reasons such as price, accessibility or the specific effects procured by certain NPS. The results showed as well that a majority of NPS users seem to be aware of the substances they are using. Conclusion Understanding the motivations of use is of importance to determine which type of NPS targeted interventions are adapted to different profiles of users.

Aerial parts containing cannabidiol can be purchased in a legal way but cannabis used as recreational drug is illegal in most European countries. Δ9-tetrahydrocannabinol is one of the main cannabinoids responsible for the psychotropic effect. European Union countries and Switzerland authorize a concentration of THC of 0.2 % and 1.0 % w/w, respectively, for smoking products and industrial hemp. Public health inspectors and law enforcement officers need to check the legality of samples. Therefore there is a need for innovative approaches, allowing quality control of these products in an easy way and preferably on site. In many countries, cultivation of industrial hemp is permitted if the THC content does not exceed 0.2 % w/w. A portable equipment could be a useful measuring tool for farmers to check for the THC content at regular time. In this work, 189 samples were analysed with a benchtop and a handheld NIR device in order to create two classification methods according to European and Swiss laws. All samples were also analysed by GC-FID to determine their THC concentration. Supervised analysis was applied in order to establish the best model. For the first classification, the accuracy was 91% for the test set with the benchtop data and 93 % for the test set with the handheld data. For the second classification, the accuracies were respectively 91 % and 95 %. The obtained models, hyphenating spectroscopic techniques and chemometrics, enable to discriminate legal and illegal cannabis samples according to European and Swiss laws.

More and more events, such as the summer music festivals, are considering the possibilities for implementing on-site testing of psychoactive drugs in the context of prevention and harm reduction. Although the on-site identification is already implemented by plenty of drug checking services, the required rapid quantitative dosing of the composition of illicit substances is still a missing aspect for a successful harm reduction strategy at events. In this paper, an approach is presented to identify white powders as amphetamine, cocaine, ketamine or others and to estimate the purity of the amphetamine, cocaine and ketamine samples using spectroscopic techniques hyphenated with partial least squares (PLS) modelling. For identification purposes, it was observed that mid-infrared spectroscopy hyphenated with PLS-discriminant analysis allowed the distinction between amphetamine, cocaine, ketamine and other samples and this with a correct classification rate of 93.1% for an external test set. For quantitative estimation, near-infrared spectroscopy was more performant and allowed the estimation of the dosage/purity of the amphetamine, cocaine and ketamine samples with an error of more or less 10% w/w. An easily applicable, practical and cost-effective approach for on-site characterisation of the majority of the psychoactive samples encountered in Belgian nightlife settings based on IR spectroscopy was proposed.

E-cigarettes have become very popular, a trend that has been stimulated by the wide variety of available e-liquid flavours. Considering the large number of e-liquid flavours (>7000), there is an urgent need to establish a screening strategy to prioritize the flavouring substances of highest concern for human health. In the present study, a prioritization strategy combining analytical screening, in silico tools and literature data was developed to identify potentially genotoxic e-liquid flavourings. Based on the analysis of 129 e-liquids collected on the Belgian market, 60 flavourings with positive in silico predictions for genotoxicity were identified. By using literature data, genotoxicity was excluded for 33 of them whereas for 5, i.e. estragole, safrole, 2-furylmethylketon, 2,5-dimethyl-4-hydroxyl-3(2H)-furanone and transhexanal, there was a clear concern for in vivo genotoxicity. A selection of 4 out of the remaining 22 flavourings was tested in two in vitro genotoxicity assays. Three out of the four tested flavourings induced gene mutations and chromosome damage in vitro, whereas equivocal results were obtained for the fourth compound. Thus, although there is a legislative framework which excludes the use of CMR compounds in e-liquids, flavourings of genotoxic concern are present and might pose a health risk for e-cigarette users.

Advances in biotechnology and the chemical synthesis of peptides have made biopharmaceuticals and synthetic peptide drugs viable pharmaceutical compounds today and an important source for tomorrow's drugs and therapies. Unfortunately, also falsifications and counterfeit versions of these powerful and promising drugs are offered illegally via the internet. Since these falsified preparations are produced outside the legally required quality systems, end-users have no guarantee regarding the efficacy and safety of these products. Although falsified samples of biotherapeutics were already analysed, looking at a specific aspect of their quality or identity, no systematic studies have been performed regarding the presence of different impurities or possible contaminations. Therefore, in order to obtain a better understanding of the potential health risks related to the usage of falsified polypeptide drugs we performed a systematic screening of the ten most frequently encountered falsified peptide drugs on the Belgian market acquired from three different suspected illegal internet pharmacies. The screening incorporated the analysis of the active pharmaceutical ingredient (API), API-related impurities, small molecule contaminants (defined as organic small molecules not belonging to the other categories), elemental impurities and residual solvents. This comprehensive study showed that these type of falsified drugs not only have a high variation in amount of drugs per unit and a low purity (ranging between 5% and 75% for cysteine containing peptides), but also contained the known toxic class one elemental impurities arsenic (As) and lead (Pb). One sample was contaminated with Pb while multiple samples were found with concentrations up to ten times the ICH toxicity limit for parenteral drugs. Subsequent speciation of As confirmed the elevated concentrations for As and demonstrated that all As was present in the more toxic inorganic form. Together with the (sometimes) high amount of peptide impurities and the inherent dangers associated with the use of unauthorized peptide drugs (such as doping peptides or preclinical drugs) this study confirms the reported potential health risks patients/users take when resorting to falsified peptide drugs. Moreover, the presence of the carcinogen As and the known accumulation in human tissues of Pb raises questions about potential sub-acute to chronic toxicity due to the long term administration of these falsified peptide drugs.

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.