Systematic analytical characterization of new psychoactive substances: A case study

AbstractNew psychoactive substances (NPS) are synthesized compounds that are not usually covered by European and/or international laws. With a slight alteration in the chemical structure of existing illegal substances registered in the European Union (EU), these NPS circumvent existing controls and are thus referred to as “legal highs”. They are becoming increasingly available and can easily be purchased through both the internet and other means (smart shops). Thus, it is essential that the identification of NPS keeps up with this rapidly evolving market.In this case study, the Belgian Customs authorities apprehended a parcel, originating from China, containing two samples, declared as being “white pigments”. For routine identification, the Belgian Customs Laboratory first analysed both samples by gas-chromatography mass-spectrometry and Fourier-Transform Infrared spectroscopy. The information obtained by these techniques is essential and can give an indication of the chemical structure of an unknown substance but not the complete identification of its structure. To bridge this gap, scientific and technical support is ensured by the Joint Research Centre (JRC) to the European Commission Directorate General for Taxation and Customs Unions (DG TAXUD) and the Customs Laboratory European Network (CLEN) through an Administrative Arrangement for fast recognition of NPS and identification of unknown chemicals. The samples were sent to the JRC for a complete characterization using advanced techniques and chemoinformatic tools.The aim of this study was also to encourage the development of a science-based policy driven approach on NPS.These samples were fully characterized and identified as 5F-AMB and PX-3 using 1H and 13C nuclear magnetic resonance (NMR), high-resolution tandem mass-spectrometry (HR-MS/MS) and Raman spectroscopy. A chemoinformatic platform was used to manage, unify analytical data from multiple techniques and instruments, and combine it with chemical and structural information

Rheological characterization of xanthan gum and hydroxypropylmethyl cellulose with respect to controlled-release drug delivery

It has been observed previously that xanthan gum (XG) and hydroxypropylmethyl cellulose (HPMC) show different drug release behavior. In order to clarify these findings, the rheological properties of both polymers have been determined by oscillatory as well as by steady shear measurements. Aqueous solutions of 4 and 7% (w/w) polymer have been used to simulate the outer surface of a hydrated tablet. The dynamic moduli, i.e., storage modulus (G') and loss modulus (G'') of the two polymers have been determined in pure water and USP phosphate buffer pH 7.4 at different dilutions. In this concentration range XG solution exhibits ''gel-like'' behavior, while HPMC behaves as a typical polymer solution. These findings are quite consistent with the reported higher ability of XG matrices to retard drug release than HPMC matrices for controlled-release formulation. The effects of differences in drug solubility and acidity, as well as the addition of lactose, and of the ionic strength of the medium on the rheological properties of XG and HPMC solutions have been studied in detail. Among these parameters, only the salt concentration exerts an enhancing effect on both moduli of XG, while no detectable influence on HPMC solution could be observed.status: publishe

Ozon: eerst denken, dan doen

LES 80status: publishe

Microstructural analysis and rheology of immiscible polymer blends

SIGLEAvailable from KULeuven, Campusbib. Exacte Wetenschappen, Celestijnenlaan 300A, 3001 Heverlee, Belgium / UCL - Université Catholique de LouvainBEBelgiu

Inulin hydrogels as carriers for colonic drug targeting. Rheological characterization of the hydrogel formation and the hydrogel network

Free radical polymerization converts aqueous solutions of methacrylated inulin into cross-linked hydrogels. The purpose of this work was to study the hydrogel formation and to characterize the fully cured hydrogels. The gelation process of aqueous solutions of methacrylated inulin was monitored as a function of time by means of linear oscillatory shear measurements, at a fixed frequency and amplitude. The fully cured inulin hydrogels were characterized by measurement of the frequency-dependency of the linear elastic modulus G'. The effects of the degree of substitution and feed concentration of methacrylated inulin on both the gelation kinetics and the rigidity of the obtained hydrogels were determined. The effect of the concentration of the initiators of the radical polymerization reaction has been studied as well. The weight fraction of polymer which was not incorporated in the hydrogel networks was determined using the anthrone reaction, and physical chain entanglements were determined by solution viscosity measurements. The gelation kinetics and the elastic modulus were proportional to the degree of substitution and feed concentration of methacrylated inulin. Increasing concentrations of radical-forming compounds also accelerated the hydrogel formation, but lowered the elastic modulus of the obtained hydrogels. The amount of polymer chains incorporated in the hydrogel network seemed to be especially influenced by the degree of substitution of the derivatized inulin, and for a feed concentration of 27% w/w of methacrylated inulin, entanglements have to be accounted for. The gelation kinetics and the elastic modulus of inulin hydrogels are not only affected by the degree of substitution and the feed concentration of methacrylated inulin, but also by the concentration of the initiators of the free radical polymerization reaction.status: publishe

Cannabinoid receptor activation potential of the next generation, generic ban evading OXIZID synthetic cannabinoid receptor agonists

In recent years, several nations have implemented various measures to control the surge of new synthetic cannabinoid receptor agonists (SCRAs) entering the recreational drug market. In July 2021, China put into effect a new generic legislation, banning SCRAs containing one of seven general core scaffolds. However, this has driven manufacturers towards the synthesis of SCRAs with alternative core structures, exemplified by the recent emergence of "OXIZID SCRAs." Here, using in vitro beta-arrestin2 recruitment assays, we report on the CB1 and CB2 potency and efficacy of five members of this new class of SCRAs: BZO-HEXOXIZID, BZO-POXIZID, 5-fluoro BZO-POXIZID, BZO-4en-POXIZID, and BZO-CHMOXIZID. All compounds behaved as full agonists at CB1 and partial agonists at CB2. Potencies ranged from 84.6 to 721 nM at CB1 and 2.21 to 25.9 nM at CB2. Shortening the n-hexyl tail to a pentyl tail enhanced activity at both receptors. Fluorination of this pentyl analog did not yield a higher receptor activation potential, whereas an unsaturated tail resulted in decreased potency and efficacy at CB1. The cyclohexyl methyl analog BZO-CHMOXIZID was the most potent compound at both receptors, with EC50 values of 84.6 and 2.21 nM at CB1 and CB2, respectively. Evaluation of the activity of a seized powder containing BZO-4en-POXIZID suggested a high purity, in line with high-performance liquid chromatography coupled to diode-array detection (HPLC-DAD), gas chromatography coupled to mass spectrometry (GC-MS), liquid chromatography coupled to time-of-flight mass spectrometry (LC-QTOF-MS), and Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) analysis. Furthermore, all tested compounds showed a preference for CB2, except for BZO-POXIZID. Overall, these findings inform public health officials, law enforcement agencies, and clinicians on these newly emerging SCRAs