Caio Henrique Pinke Rodrigues

Abstract: Identifying new psychoactive substances in a reliable manner is an exciting idea in forensic science. In this work, we apply in silico methods to recognize classes of drugs. We calculate the infrared spectra of 21 pairs of amphetamine and cathinone homologs by in silico techniques and compare the theoretical data with the experimental data. First, we submit each molecule to conformational analysis and use the minimum energy structure to determine the frequencies that generate the infrared spectra. We employ three different Density Functional Methods –B3LYP, B3LYP-D3 and M06-2X– and the 6-31G∗∗ basis set implemented on Gaussian 09 for this purpose. Application of supervised and unsupervised multivariate classification methods to the spectra helps us to evaluate the theoretical results. The in silico procedure adopted herein can predict the infrared values and provides valuable information about unknown substances. Therefore, this methodology could help to create an effective tool to identify unknown psychoactive substances.

Abstract: 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.

Abstract: Given the fast-growing demand for anti-trafficking measures, this article investigates the development of voltammetric sensors for the oxidation of cocaine hydrochloride on the surface of carbon paste electrodes chemically modified with Schiff base complexes and their potential use for cocaine detection and quantification in seized samples. Voltammetric analyses revealed that [CoII(salen)] displayed amperometric and thermal stability, was uniformly distributed on the electrode surface, was only degraded at temperatures above 300 °C, and did not undergo passivation in acid medium. The [CoII(salen)]-modified voltammetric sensor gave error below 10%, an improvement on HPLC. SIMCA chemometric analyses predicted the group belonging to cocaine hydrochloride and its interferents effectively, attesting to the good selectivity and specificity of the developed sensor. The sensor has potential application in forensic investigations: its LOD and LOQ, intra and inter-day precision, accuracy, linearity ranges, selectivity, specificity, and sensitivity are better as compared to other chemically modified electrodes. Finally, the Density Functional Theory (DFT) method confirmed the oxidation–reduction mechanisms proposed in the literature.

Abstract: The amount and variety of new psychoactive substances (NPS) are expanding, and there are difficulties in assessing their risks. In this regard, in silico methods are potentially useful to predict NPS properties faster and at a lower cost. In this work a quantitative structure-activity relationship (QSAR) model was used to verify the risk of drugs derived from amphetamines and cathinones. A dataset of 26 derivatives with in vitro affinity for norepinephrine transporter (NET) was selected. To ensure reproducibility of the results, only geometric molecular descriptors (AM1 (Austin model 1) level) obtained from the platform ChemDes and ordered predictors selection (OPS) were used. The model presents good internal statistics (n = 23; coefficient of determination (R2) = 0.914). The small number of samples was divided into seven training sets (n = 17) and seven test sets (n = 6). The average R2pred = 0.754 showed that the model has good predictive capacity. Based on the tests, this model can accurately predict the risk range of three previously selected derivatives: methedrone (low), ethcathinone (medium), and methamphetamine (high), even when only data referring to NET are employed. We used these data to create a simple free program in Java that focuses on the risk assessment of recreational drugs belonging to this class of compounds.

Abstract: A detailed description is given of the development and validation of a fully automated in-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC–MS/MS) method capable of detecting 90 central-stimulating new psychoactive substances (NPS) and 5 conventional amphetamine-type stimulants (amphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-N-ethyl-amphetamine (MDEA), methamphetamine) in serum. The aim was to apply the validated method to forensic samples. The preparation of 150μL of serum was performed by an Instrument Top Sample Preparation (ITSP)-SPE with mixed mode cation exchanger cartridges. The extracts were directly injected into an LC–MS/MS system, using a biphenyl column and gradient elution with 2mM ammonium formate/0.1% formic acid and acetonitrile/0.1% formic acid as mobile phases. The chromatographic run time amounts to 9.3min (including re-equilibration). The total cycle time is 11min, due to the interlacing between sample preparation and analysis. The method was fully validated using 69 NPS and five conventional amphetamine-type stimulants, according to the guidelines of the Society of Toxicological and Forensic Chemistry (GTFCh). The guidelines were fully achieved for 62 analytes (with a limit of detection (LOD) between 0.2 and 4μg/L), whilst full validation was not feasible for the remaining 12 analytes. For the fully validated analytes, the method achieved linearity in the 5μg/L (lower limit of quantification, LLOQ) to 250μg/L range (coefficients of determination>0.99). Recoveries for 69 of these compounds were greater than 50%, with relative standard deviations≤15%. The validated method was then tested for its capability in detecting a further 21 NPS, thus totalling 95 tested substances. An LOD between 0.4 and 1.6μg/L was obtained for these 21 additional qualitatively-measured substances. The method was subsequently successfully applied to 28 specimens from routine forensic case work, of which 7 samples were determined to be positive for NPS consumption.

Abstract: 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.

Abstract: Synthetic cannabinoids (SC’s) began to gain popularity around the world in 2009. Since then, many of the compounds have been outlawed and methods developed to detect them and their metabolites using mass spectrometry. Our work investigated the possibility of developing a colorimetric presumptive test. The SC JWH-019 was synthesized and its ketone targeted as a possible reaction site. Many SC’s contain ketones and thus a reaction at this site would be applicable to many of the compounds. Since JWH-019 is costly and time consuming to synthesize, much of the experimental work was done using benzophenone (BP). BP contains a diaryl ketone making it comparable to JWH-019. Our initial work studied existing presumptive tests, one for SC’s and one for cannabis. Both gave negative results for JWH-019. From there, we looked at synthesizing imines that might be colored. We studied reactions using dinitrophenylhydrazone, hydrazine, aniline and neutral red. Through these reactions it became apparent that the ketones on BP and JWH-019 were reluctant to react. Finally, we studied forming imines of BP with either ethylenediamine (en) or semicarbazide. The resulting product was then used to produce a metal complex. A complex formed between the en-BP product and Cu 2+ provided a change in color, but the en-BP imine proved difficult to obtain and the results were not consistent.