Sulaf Assi

Phenomenon of new drugs on the Internet: The case of ketamine derivative methoxetamine

On the basis of the material available both in the scientific literature and on the web, this paper aims to provide a pharmacological, chemical and behavioural overview of the novel compound methoxetamine. This is a dissociative drug related to ketamine, with a much longer duration of action and intensity of effects. A critical discussion of the availability of information on the web of methoxetamine as a new recreational trend is here provided. Those methodological limitations, which are intrinsically associated with the analysis of online, non‐peer reviewed, material, are here discussed as well. It is concluded that the online availability of information on novel psychoactive drugs, such as methoxethanine, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast‐growing phenomenon. Copyright

From "Special K" to "Special M": the evolution of the recreational use of ketamine and methoxetamine.

This article reviews the recreational use of ketamine (“Special K”; KET) and explores the recent diffusion of its new derivative methoxetamine (“Special M”; MXE). The literature search on the nonclinical/recreational use of KET and MXE was carried out in a range of medical databases. Considering the limitations of peer‐reviewed information, data were integrated with a qualitative assessment of a range of websites, drug fora, and other online resources including e‐newsgroups, chat rooms, mailing lists, e‐newsletters, and bulletin boards. The recreational use of KET has started since its discovery in 1962. This was due to its rapid onset, short duration of action, and peculiar psychotropic effects (“K‐hole”). The latter effect ranges from confusion to dissociation and depersonalization (near‐death experience). However, KET abuse is often associated with physical and psychological side effects, of which the worst is urological/bladder toxicity. Recently, MXE has emerged as a legal and “bladder‐friendly” KET alternative. MXE presents with the same dissociative effect of KET, but with slower onset and longer duration of action. However, MXE seems to be associated with worse side effects than KET, ranging from mood disturbances/suicidal attempts to acute cerebellar toxicity. After 50 years of its discovery, KET has led to the emergence of MXE. However, this latter derivative does not appear to be a safer alternative to KET itself.

Promoting innovation and excellence to face the rapid diffusion of Novel Psychoactive Substances in the EU: the outcomes of the ReDNet project

The recent emergence of new psychoactive compounds (novel psychoactive substances (NPS)) has raised prominent challenges in the fields of drug policy, substance use research, public health and service provision. The Recreational Drugs European Network project, funded by the European Commission, was implemented to improve the information stream to young people and professionals about effects/risks of NPS by identifying online products and disseminating relevant information through technological tools.

5,6-Methylenedioxy-2-aminoindane: from laboratory curiosity to 'legal high'.

The fully synthetic ‘legal high’ 5,6‐methylenedioxy‐2‐aminoindane (MDAI) is an analogue of 3,4‐methylenedioxymethamphetamine. Although developed in the 1990s, it was not widely abused until 2010. However, mephedrone was banned in the UK in April 2010, and almost immediately, MDAI was widely advertised as a legal alternative. This paper provides both an overview of the current state of knowledge of MDAI and a critical analysis of online available information relating to its psychoactive effects, adverse reactions and use in combination with other drugs.

Identifying counterfeit medicines using near infrared spectroscopy

Counterfeit medicines are a growing threat to public health across the world and screening methods are needed to allow their rapid identification. A counterfeiter must duplicate both the physical characteristics and the chemical content of a proprietary product to avoid it being detected as a counterfeit product and this is almost impossible to get right. Counterfeit proprietary medicines are, therefore, relatively easy to identify by near infrared (NIR) spectroscopy which can detect physical as well as chemical differences between products by simple spectral comparison. Identifying generic products is more difficult as they use different excipients in the tablet or capsule matrix. Nevertheless, using appropriate models and a large library, NIR spectroscopy can detect counterfeit generic versions. Detecting sub-standard proprietary medicines can be carried out with NIR spectroscopy models and the most widely used is partial least squares regression (PLSR). General rules for generating accurate quantitative models are easy to describe. Quantifying the active pharmaceutical ingredient (API) in generic products can also be carried out using PLSR models with calibration samples generated by manufacturing laboratory samples or by collecting many generic versions of a medicine so as to obtain a good range of the API content in tablets and capsules. Using hand-held instruments or mobile laboratories allows NIR spectrometers to be taken to places where analyses may be made quickly, rather than taking the samples to a laboratory. This has the enormous advantage that the screening of large numbers of samples may be made in pharmacies and wholesalers. Imaging can bring a whole new dimension to NIR spectroscopy to allow the identification of the API and individual excipients as well as measuring the particle sizes of components and giving a measure of the homogeneity of the matrix. The effect of water on potential misidentifications may be obviated by only using blister-packed samples, having large spectral libraries subjected to different humidities or omitting the spectral region where water absorbs.

Nitrogen-14 Nuclear Quadrupole Resonance Spectroscopy: A Promising Analytical Methodology for Medicines Authentication and Counterfeit Antimalarial Analysis

We report the detection and analysis of a suspected counterfeit sample of the antimalarial medicine Metakelfin through developing nitrogen-14 nuclear quadrupole resonance ((14)N NQR) spectroscopy at a quantitative level. The sensitivity of quadrupolar parameters to the solid-state chemical environment of the molecule enables development of a technique capable of discrimination between the same pharmaceutical preparations made by different manufacturers. The (14)N NQR signal returned by a tablet (or tablets) from a Metakelfin batch suspected to be counterfeit was compared with that acquired from a tablet(s) from a known-to-be-genuine batch from the same named manufacturer. Metakelfin contains two active pharmaceutical ingredients, sulfalene and pyrimethamine, and NQR analysis revealed spectral differences for the sulfalene component indicative of differences in the processing history of the two batches. Furthermore, the NQR analysis provided quantitative information that the suspected counterfeit tablets contained only 43 ± 3%, as much sulfalene as the genuine Metakelfin tablets. Conversely, conventional nondestructive analysis by Fourier transform (FT)-Raman and FT-near infrared (NIR) spectroscopies only achieved differentiation between batches but no ascription. High performance liquid chromatography (HPLC)-UV analysis of the suspect tablets revealed a sulfalene content of 42 ± 2% of the labeled claim. The degree of agreement shows the promise of NQR as a means of the nondestructive identification and content-indicating first-stage analysis of counterfeit pharmaceuticals.

Analysis of ‘legal high’ substances and common adulterants using handheld spectroscopic techniques

The identification of ‘legal highs’ is challenging as they often do not match their label claim and contain a wide range of impurities and/or adulterants. In addition, there is a need for techniques to be on-site, rapid and non-destructive. The feasibility of using the in-built algorithms of handheld near-infrared (NIR), Raman and attenuated total reflectance Fourier transform-infrared (ATR-FT-IR) spectroscopy for the identification of ‘legal high’ substances was investigated. Spectral libraries were constructed using three substances found in ‘legal highs’ (i.e., dextromethorphan, 2-aminoindane and lidocaine) and their 50 : 50 mixtures with caffeine. Model dilution mixtures with caffeine (i.e., 5–95% m/m) and seven ‘legal high’ Internet products were used to test the method. The ‘legal high’ constituents in most of the model mixtures were identified within a minimum range of 30–60% m/m for NIR, 20–75% m/m for Raman, and 41–85% m/m for ATR-FT-IR. This demonstrates that simple library mixtures could be used to identify test substances when the concentrations are variable. Below and above these levels, the test mixtures often correlated to the component in higher concentration. Collectively, the instruments identified the main constituents in the seven Internet products with varying correlation criteria. The NIR and ATR-FT-IR provided complementary information compared to Raman when carbohydrate cutting agents were added to the product, yet the Raman showed a high fluorescence signal for three products hindering identification. These initial studies indicate the suitability of three complementary techniques for rapid identification of ‘legal high’ products. Further development of spectral libraries, algorithms, and use of alternative Raman excitation wavelengths is needed to provide adequate tools for in-field analysis by non-experts.

Identification of counterfeit medicines from the Internet and the World market using near-infrared spectroscopy

Pharmaceutical counterfeiting is a life threatening problem affecting all countries. Counterfeit medicines may be encountered anywhere in conventional markets or from the Internet. This paper proposes a rapid and non-destructive near-infrared spectroscopic method for the identification of counterfeit medicines using the minimum number of authentic samples. As little as twenty spectra from ten tablets from a batch are required to compare a test sample to its authentic counterpart. In this respect, tablets are measured as received and the correlation coefficient of the SNV-D2 spectra between the authentic sample and the test sample is determined. A correlation coefficient of lower than 0.95 indicates that the batch fails identification. In this case, if enough authentic samples are available, principal component analysis (PCA) could be applied. The PCA scores plot of the authentic and counterfeit samples with the 95% equal frequency ellipses drawn around the authentic sample set is effective in identifying counterfeits. The method could identify 82 known counterfeit medicines out of 201 medicines supplied from the Internet and the World market. However, it is still a comparative method to identify potential counterfeits and cannot identify products without authentic samples.

Profile, effects, and toxicity of novel psychoactive substances: A systematic review of quantitative studies

To investigate the profile, effects, and toxicity of novel psychoactive substances (NPS).

Swift Quantification of Fenofibrate and Tiemonium methylsulfate Active Ingredients in Solid Drugs Using Particle Induced X-Ray Emission

The quantification of active ingredients (AI) in drugs is a crucial and important step in the drug quality control process. This is usually performed by using wet chemical techniques like LC-MS, UV spectrophotometry and other appropriate organic analytical methods. However, if the active ingredient contains specific heteroatoms (F, S, Cl…), elemental IBA like PIXE and PIGE techniques, using small tandem accelerator of 1-2 MV, can be explored for molecular quantification. IBA techniques permit the analysis of the sample under solid form, without any laborious sample preparations. In this work, we demonstrate the ability of the Thick Target PIXE technique for rapid and accurate quantification of both low and high concentrations of active ingredients in different commercial drugs. Fenofibrate, a chlorinated active ingredient, is present in high amounts in two different commercial drugs, its quantification was done using the relative approach to an external standard. On the other hand, Tiemonium methylsulfate which exists in relatively low amount in commercial drugs, its quantification was done using GUPIX simulation code (absolute quantification) The experimental aspects related to the quantification validity (use of external standards, absolute quantification, matrix effect,...) are presented and discussed.