Irgafos 168 and Irganox 1076 as new cocaine cutting agents: A COVID-19 pandemic impact on cocaine profiling and trafficking in Brazil.

BACKGROUNDS: Restrictions in movement and closure of borders imposed by the Sars-Cov- 2 worldwide pandemic have affected the global illicit drug market, including cocaine trafficking. In this scenario, comparing cutting agents added to the cocaine and the drug purity are valuable strategies to understand how the drug trade has been impacted by the pandemic. METHODS: In this work, 204 cocaine salt materials seized in the Brazilian Federal District, before (2019) and during COVID-19 pandemics (2020) were analyzed by two analytical techniques: gas chromatography-mass spectrometry (GC-MS) and Fourier-transform infrared spectroscopy (FTIR). Statistical analyses, including Principal Component Analysis (PCA), were applied to evaluate the COVID-19 pandemic impact in the local market. Bibliometric analysis was performed as a forensic intelligence tool. RESULTS: From 2019-2020, cocaine average purity decreased 26 % while the frequency of cutting agents, as caffeine and anesthetics (lidocaine, tetracaine) increased. The high percentage of unknown were increased. Different cocaine profiling seized in 2020 showed new cutting agents, such as Irganox 1076, and Irgafos 168, indicating a trend on new adulterants/diluents introduced in the local market to mitigate the local drug shortage. Also in 2020, there was an increase in the local cocaine seizures, despite of the cocaine drug purity decreased by 26 % compared to 2019. CONCLUSIONS: Taken together, these data showed that the covid-19 pandemics has impacted cocaine trafficking in the Brazilian Federal District, an increase in cocaine seizures, which may indicate greater demand for the drug and, specially, changes in the cocaine purity and cutting agents profiling showing how traffickers tried to minimize difficulties in crossing the Brazilian border during COVID-19 restrictions. The information is relevant since Brazil is one of the major departure points for traded cocaine to the world. Bibliometric analysis showed that Irgafos 168 and Irganox 1076 were consistently identified as cocaine cutting agents for the first time.

Fragment-guided approach to incorporating structural information into a CoMFA study: BACE-1 as an example.

Alzheimer's disease is an ultimately fatal neurodegenerative disease, and BACE-1 has become an attractive validated target for its therapy, with more than a hundred crystal structures deposited in the PDB. In the present study, we present a new methodology that integrates ligand-based methods with structural information derived from the receptor. 128 BACE-1 inhibitors recently disclosed by GlaxoSmithKline R&D were selected specifically because the crystal structures of 9 of these compounds complexed to BACE-1, as well as five closely related analogs, have been made available. A new fragment-guided approach was designed to incorporate this wealth of structural information into a CoMFA study, and the methodology was systematically compared to other popular approaches, such as docking, for generating a molecular alignment. The influence of the partial charges calculation method was also analyzed. Several consistent and predictive models are reported, including one with r (2) = 0.88, q (2) = 0.69 and r (pred) (2)  = 0.72. The models obtained with the new methodology performed consistently better than those obtained by other methodologies, particularly in terms of external predictive power. The visual analyses of the contour maps in the context of the enzyme drew attention to a number of possible opportunities for the development of analogs with improved potency. These results suggest that 3D-QSAR studies may benefit from the additional structural information added by the presented methodology.

Analysis of non-derivatized 2-(4-R-2,5-dimethoxyphenyl)-N-[(2-hydroxyphenyl)methyl]ethanamine using short column gas chromatography - mass spectrometry.

The 25R-NBOH family is a group of thermally labile compounds that are relevant for forensic sciences and traditionally analyzed by GC-MS after derivatization - a step that is time consuming in a routine work. In this paper, the use of short analytical columns (4 and 10 m) showed to decrease compound degradation in the GC oven during chromatographic separation and to allow the analysis of non-derivatized 25R-NBOH compounds by GC-MS. A shorter column demanded a higher gas flow rate, and both factors decreased residence time of the analytes in the column and their degradation. The inlet temperature (250° C or 280°C) did not impact the response of 25R-NBOH. A 25R-NBOH fragmentation pathway by electron ionization was also presented for the first time. The GC-MS method with a 4 m column was successfully applied to other compounds of forensic interest, and it can be tested in the analysis of biological samples in toxicological investigations.

Formaldehyde analysis of seized cosmetic products by HS-GC-MS of methylal, ethoxymethoxymethane, and ethylal derivatives

Abstract Formaldehyde is a carcinogenic compound used as preservative in cosmetic products. In this study, a derivatization procedure using MeOH, EtOH and HCl (25:25:1), and incubation at 60ºC for 4 hours was optimized, and the derivatized products - methylal, ethoxymethoxymethane (EMM), and ethylal - were directly analyzed by headspace-gas chromatography-mass spectrometry (HS-GC-MS) to determine formaldehyde concentrations. The validated method provided good linearity of the standard curve, selectivity, recovery (89.6-106.6%), repeatability, and intermediate precision (RSD < 12%), with an LOD of 0.0015% and an LOQ of 0.005% for all derivatized analytes. The validated method showed to be fast, clean, and easy to implement in a laboratory. To the best of our knowledge, this is the first reported HS-GC-MS procedure to determine formaldehyde as methylal, ethylal, and EMM as derivatized compounds. The method was satisfactorily applied for the analysis of nine hair-straightener cream samples seized by the Civil Police of the Federal District, Brazil. Eight samples contained formaldehyde, at levels ranging from 0.33 to 4.02 %, higher than the legal levels, indicating the need to control the levels of this toxic compound in cosmetic products

A fragment-based approach for ligand binding affinity and selectivity for the liver X receptor beta.

Selective modulation of liver X receptor beta (LXRß) has been recognized as an important approach to prevent or reverse the atherosclerotic process. In the present work, we have developed robust conformation-independent fragment-based quantitative structure-activity and structure-selectivity relationship models for a series of quinolines and cinnolines as potent modulators of the two LXR subtypes. The generated models were then used to predict the potency of an external test set and the predicted values were in good agreement with the experimental results, indicating the potential of the models for untested compounds. The final 2D molecular recognition patterns obtained were integrated to 3D structure-based molecular modeling studies to provide useful insights into the chemical and structural determinants for increased LXRß binding affinity and selectivity.