Analytical challenges for identification of new psychoactive substances: a literature-based study for seized drugs

Correct identification of substances is essential to understand drug use and trafficking trends and guide measures for harm reduction and treatment. Two steps are needed to verify the nature of a substance properly: a presumptive test and a confirmatory test. There are presumptive tests which presents deficiencies, such as providing false-positive and false-negative results. Confirmatory tests are more reliable but they are more expensive. With the appearance of New Psychoactive Substances (NPS), identifying and characterizing illicit substances has become more challenging. This paper focuses on presenting information about NPS characteristics and analysis. For this purpose, we have reviewed the literature to address the main aspects of five groups of NPS: amphetamine-type stimulants, synthetic cannabinoids, N-methoxybenzyl-methoxyphenylethylamine (NBOMe), synthetic opioids, and benzodiazepines. We present the main characteristics of each group and certain aspects of presumptive and confirmatory tests regarding these groups. Our findings show obstacles in developing methodologies that can correctly identify these substances, and problems can increase as new structures appear. This information can be helpful to drive research into identifying NPS and inform law enforcement and law practitioners about the main characteristics of each group and the main questions involving their identification

Theoretical study of synthetic opioids in the context of the new psychoactive substances

Substâncias análogas sintéticas do fentanil que não foram aprovadas para uso médico são conhecidas como fentanis não farmacêuticos (NPF, Non-Pharmaceutical Fentanyls). Sua síntese clandestina envolve a modificação química de um medicamento existente, que pode ter efeitos farmacológicos imprevisíveis. Essas mudanças também tornam a identificação química difícil. Como novas estruturas estão surgindo em um ritmo rápido, os métodos experimentais usados para caracterizar essas substâncias não conseguem acompanhar esse ritmo. Nesse cenário, os métodos in silico tornaram-se uma alternativa para estudar esses sistemas. Neste trabalho aplicamos o planejamento fatorial para decidir as melhores condições relacionadas a métodos de teoria do funcional da densidade (DFT, Density Functional Theory) para realizar os cálculos. O método que apresentou os melhores resultados foi o conjunto B3LYP, 6-311G**, LooseSCF e NormalOpt, pois reproduziu de maneira satisfatória as estruturas experimentais utilizadas para comparação. Essas condições foram usadas para calcular o espectro infravermelho de 45 NPF apreendidos reportados na literatura. Os espectros calculados foram validados por comparação com dados experimentais e têm potencial, portanto, de servirem como uma referência para compostos desconhecidos. Métodos quimiométricos foram utilizados para estabelecer as principais características dessas substâncias de acordo com a variação estrutural. Métodos in silico também foram utilizados para estudar a tendência de comportamento biológico dessas substâncias. Para isso, utilizamos métodos de ancoragem molecular, que dão uma ideia sobre a interação dessas drogas com o receptor. Os metabólitos dessas substâncias também foram estudados por metodologia computacional e puderam ser comparados com resultados reportados na literatura. Em conclusão, os métodos in silico forneceram informações valiosas sobre substâncias ilegais. Além disso, esses métodos são úteis para prever as propriedades espectroscópicas e biológicas dos NPF e para melhorar a qualidade das informações disponíveis sobre eles.Synthetic fentanyl analog substances that have not been approved for medical use are known as Non-Pharmaceutical Fentanyls (NPF). Its clandestine synthesis involves the chemical modification of an existing drug, which can lead to unpredictable pharmacological effects. These changes also make chemical identification difficult. As new structures are emerging at a rapid rate, the experimental methods used to characterize these substances cannot keep pace. In this scenario, in silico methods have become an alternative to study these systems. In this work we apply factorial planning to decide the best conditions related to Density Functional Theory (DFT) to perform the calculations. The method that presented the best results was the B3LYP, 6-311G **, LooseSCF and NormalOpt set, as it reproduced in a satisfactory way the experimental structures used for comparison. These conditions were used to calculate the infrared spectrum of 45 apprehended NPF reported in the literature. The calculated spectra were validated by comparison with experimental data and therefore have the potential to serve as a reference for unknown compounds. Chemometric methods were used to establish the main characteristics of these substances according to the structural variation. In silico methods were also used to study the tendency of biological behavior of these substances. In this sense, we use molecular docking methods, which give an idea about the interaction of these drugs with its receptors. The metabolites of these substances were also studied by computational methodology and could be compared with results reported in the literature. In conclusion, in silico methods provided valuable information on illegal substances. In addition, these methods are useful for predicting the spectroscopic and biological properties of NPF and for improving the quality of available information about them