Cocaethylene, the in vivo product of cocaine and ethanol, is a narcotic more potent than its precursors.

The molecular conformation and supramolecular architecture of cocaethylene [systematic name: ethyl (1R,2R,3S,5S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate], C18H23NO4, have been determined for the first time. Cocaethylene is a narcotic produced in vivo when cocaine and ethanol are administered concomitantly. The intra- and intermolecular features of cocaethylene and its less potent narcotic precursor cocaine are very similar. The only molecular difference is in the conformation of the methyl group of the ethoxycarbonyl group. Similar to cocaine, the carboxylate atoms and the α-C atom are coplanar in cocaethylene, but the methyl C atom of the ethyl group is bent by ca 90° away from this plane in the narcotic reported here. The main supramolecular motif is a one-dimensional chain stabilized by weak C-H...O contacts.

A survey of adulterants used to cut cocaine in samples seized in the Espírito Santo State by GC-MS allied to chemometric tools.

Cocaine is a stimulant drug of the central nervous system (CNS) extracted from the leaves of Erytroxylum coca. It is defined as a tropane alkaloid containing 1R-(exo,exo)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl esther. However, despite its defined composition, a wide variety of chemical additives are present in cocaine found in the illicit market, such as benzocaine, lidocaine, caffeine, procaine and phenacetin. In this work, 512 cocaine samples seized by the Civil Police of Espirito Santo state (PC-ES, Brazil) were analyzed by gas chromatography mass spectrometry (GC-MS) allied to principal component analysis (PCA) in order to classify the samples as a function of seizure year (2008, 2009, 2010, 2011 and 2012) and location (metropolitan, north, south and central). The cocaine content (wt.%) and its adulterants were also estimated. Analyzing the samples seized between 2008 and 2011, three sample sets are clearly grouped according to the degree of adulteration with caffeine and lidocaine: 100-50 wt.% of cocaine; 50-20 wt.% of cocaine; and 20-80 wt.% of lidocaine and 60-80 wt.% of caffeine, simultaneously. The last group is formed by samples seized between 2008 and 2009, which proves the higher degree of adulteration during this period. In 2012, higher cocaine content was observed for the 191 analyzed samples than in samples from previous years. The PCA data also suggests that the metropolitan region samples had a higher degree of adulteration than the state countryside samples.

Thin layer chromatography coupled to paper spray ionization mass spectrometry for cocaine and its adulterants analysis.

Thin layer chromatography (TLC) is a simple and inexpensive type of chromatography that is extensively used in forensic laboratories for drugs of abuse analysis. In this work, TLC is optimized to analyze cocaine and its adulterants (caffeine, benzocaine, lidocaine and phenacetin) in which the sensitivity (visual determination of LOD from 0.5 to 14mgmL(-1)) and the selectivity (from the study of three different eluents: CHCl3:CH3OH:HCOOHglacial (75:20:5v%), (C2H5)2O:CHCl3 (50:50v%) and CH3OH:NH4OH (100:1.5v%)) were evaluated. Aiming to improve these figures of merit, the TLC spots were identified and quantified (linearity with R(2)>0.98) by the paper spray ionization mass spectrometry (PS-MS), reaching now lower LOD values (>1.0µgmL(-1)). The method developed in this work open up perspective of enhancing the reliability of traditional and routine TLC analysis employed in the criminal expertise units. Higher sensitivity, selectivity and rapidity can be provided in forensic reports, besides the possibility of quantitative analysis. Due to the great simplicity, the PS(+)-MS technique can also be coupled directly to other separation techniques such as the paper chromatography and can still be used in analyses of LSD blotter, documents and synthetic drugs.

Analysis of cocaine and its adulterants in drugs for international trafficking seized by the Brazilian Federal Police.

Here, gas chromatography with nitrogen phosphorous detector (GC-NPD) method was developed and validated for the quantification of cocaine and adulterants (caffeine, 4-dimethylaminoantipyrine, levamisole, lidocaine and phenacetin) in illicit samples. The method was based on direct dilution of samples in methanol, sonication for 5 min and centrifugation. After appropriate dilution, an aliquot was injected into GC-MS in order to identify the active compounds and into GC-NPD for the analytes quantification. Bupivacaine was used as an internal standard. The method showed to be precise, accurate and linear over a range of 0.5-100% (weight/weight percentages) for all analytes, except phenacetin which showed a linear range between 2% and 100%. The method was successfully applied to 54 samples seized by the Brazilian Federal Police in the International Airport of Sao Paulo and mailing services during the year 2011. All the samples were associated with international trafficking and were apprehended while leaving the country. The purity of cocaine ranged from 16.5% to 91.4%. Cocaine was the only detected active compound in 29.6% of total samples. Among the identified cutting agents, levamisole was the most abundant (55.6% of the total samples) and relative concentrations (weight/weight percentages) ranged from 0.7% to 23%. Lidocaine, caffeine, phenacetin and 4-dimethylaminoantipyrine were also identified in these samples in minor concentrations. In contrast with what we initially hypothesized, drugs intended to international trafficking did not present high cocaine purity and most of the samples were laced with adulterants before leaving Brazil.

Quantitative structure-activity relationship for aromatic hydrocarbons on freshwater fish.

A quantitative structure-activity relationship (QSAR) was determined, according to Hansch's approach. The acute toxicity of nine aromatic hydrocarbons (benzene, toluene, ethylbenzene, o-xylene, m-xylene, p-xylene, isopropylbenzene, n-propylbenzene, butylbenzene) was evaluated in an Argentinean freshwater fish species. Solubility, molecular weight, and the octanol-water coefficient of partition (K(ow)) were taken as macroscopic molecular descriptors. Slopes obtained from regression analysis were similar with respect to those of the standard fish, Pimephales promelas. A potential nonpolar narcosis power (NP) concept was defined on the basis of the mode of toxic action of the assayed chemicals. Following Ferguson's principle and the critical volume doctrine for nonpolar narcosis, NP was defined as log MW*K(ow). Experimental data fitted better than regression analysis did only with log K(ow). NP improves the quantitative relationship between nonpolar narcotic compounds and their toxicity. It was more suitable to describe the physiological aspects relative to the mode of action of the chemicals assayed.

Critical comparison of extraction procedures for the capillary electrophoretic analysis of opiates in hair.

This work presents a comparative evaluation of extraction procedures for the capillary analysis of seven opiates (meperidine, morphine, naloxone, tramadol, fentanyl, sufentanyl, and alfentanyl) in human hair. Pieces of hair (50-150 mg) were subjected to acidic hydrolysis (0.25 mmol L(-1) HCl at 45 degrees C, overnight) followed by pH adjustment and either liquid-liquid extraction (LLE) in hexane, petroleum ether, dichloromethane, and ethyl acetate solvents, or solid-phase extraction (SPE) in octadecyl, cyanopropyl, and aminopropyl bonded silica and cation exchange polymeric phases. Excellent recoveries of approximately 70% (naloxone and fentanyl and its analogues), 88% (meperidine), and ca. 100% (morphine and tramadol) were obtained using SPE in a M-fixed-mode cation exchange reversed-phase cartridge (Oasis MCX LP, Waters Corp., Milford, MA, U.S.A.), making this type of procedure eligible for novel clinical and forensic methodologies for hair analysis. The utility of the proposed extraction technique was demonstrated by the analysis of hair extracts from patients using morphine as part of their pain management protocol.

Los péptidos opioides en el control del dolor / Opioid peptides in pain control

Este tabajo presenta un descripción breve de las evidencias que señalan el papel de los péptidos opioides en el control del dolor. Se describe el papel inhibidor de la ß-endorfina y de la Met-encefalina en los tejidos periféricos y, se sugiere una acción local en el sitio de la inflamación. Asimismo, se hace referencia a los sistemas endógenos de inhibición del dolor tanto a los segmentarios inherentes a la organización celular de la médula espinal, como a los sistemas descendentes, que tienen su origen en diversos núcleos del tallo cerebral. Las conexiones eferentes de estos sistemas siguen el trayecto del fascículo dorsolateral para terminar en las astas dorsales de la médula espinal, en donde ejercen su acción. Con esta idea, se analiza la participación de la ß-endorfina y los péptidos derivados en la analgesia. También se discute el papel que desempeñan los receptores µ, delta y kappa en el control del dolor y los ligandos endógenos que se unen a estos receptores. Las evidencias sugieren que la analgesia opioide, es el resultado predominante de la activación de los receptores µ, aunque los delta y los kappa pueden potenciar este efecto. Con respecto a los receptores delta y sus ligandos con mayor afinidad, las encefalinas tienen una participación indirecta en la analgesia. En relación a los receptores kappa y sus ligando más afines, las dinorfinas, los datos publicados son controvertidos. Por último, se hace referencia a los efectos paradójicos de la naloxona en el control del dolor, pues a dosis altas, aumentan las respuestas algésicas (hiperalgesia) y las dosis muy bajas producen analgesia