Toxicological Analysis of Cases of Mixed Poisonings with Synthetic Cathinones and Other Drugs of Abuse.

Some of the most commonly used new psychoactive substances (NPSs) are synthetic cathinones (SCs). The literature increasingly indicates that SCs have a significant addictive potential and pose a high risk to human health and life. The vast majority of SC users take a number of substances simultaneously. This article lists the detected concentrations in 26 fatal and 2 non-fatal real cases, in which SCs or an SC along with other substances were determined in blood and other biological materials. The following SCs were found most often: α-pyrrolidinohexiophenone, α-pyrrolidinopentiophenone, N-ethylpentedrone (NEP), 4-methyl-α-ethylaminopentiophenone and N-ethylhexedrone. In addition to detected SCs, the analyzed samples showed the presence of conventional drugs such as methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, amphetamine and NPSs from groups other than SCs, such as synthetic cannabinoids (UR-144 and 5F-AMB), synthetic opioids (AH-7921, U-47700 and 4-fluorobutyrfentanyl) and others (desoxypipradrol and etizolam). The quantitative analyses were carried out by liquid chromatography with tandem mass spectrometry (LC-MS-MS). This study presents pioneering data on concentrations and effects of 4-ethylmethcathinone, NEP, N-ethylbuphedrone and mexedrone. Also noteworthy are the data on SCs that until now have rarely been described in the literature together with specified blood concentrations. The analyzed cases of taking SCs were associated with fatal intoxication (n = 26), driving under the influence of drugs (n = 2) and death caused by beating (n = 1). Taking SCs has serious side effects that can lead to multiple organ failure and death. The use of more than one psychoactive substance simultaneously (including at least one SC) contributes to increased SC toxicity. These data could be valuable for further interpretation of other results from toxicological analyses.

Toxicological Analysis of Intoxications with Synthetic Cathinones.

Synthetic cathinones (SCs) are currently the second largest and the second most frequently seized group of new psychoactive substances. They are sold as replacements for controlled stimulants such as amphetamine, cocaine and 3,4-methylenedioxymethamphetamine. Administration of low doses of SCs can cause euphoria and increased alertness, and administration of high doses or chronic use of cathinones can cause serious adverse effects such as hallucinations, delirium, hyperthermia and tachycardia. In the years 2013-2019 in our practice, as many as 16 different SCs were detected in biological materials. This article lists the observed concentrations in 39 fatal and 18 non-fatal cases, in which a single SC as well as an SC in combination with amphetamine or ethyl alcohol were detected and quantified in biological materials. The quantitative analyses were carried out by liquid chromatography with tandem mass spectrometry. The analyzed cases of taking SCs were associated with intoxication (2 cases), fatal intoxication (36), driving under the influence of drugs (10) and other circumstances (9) such as violence, insulting an officer and holding a hostage. Taking SCs has serious side effects that can lead to multiple organ failure and death. Screening for the presence of SCs in biological materials should be part of the routine course of treatment in intoxication cases, both at the stage of clinical diagnosis and at the stage of forensic toxicological analysis. Ethyl alcohol and amphetamine may contribute to increased SC toxicity. These data could be valuable for further interpretation of other results from toxicological analyses.

Synthetic cathinones - From natural plant stimulant to new drug of abuse.

As recreational substances, synthetic cathinones started to be used at the beginning of the 21st century. There is still limited data on these compounds, introduced to the illicit drug market for the most part after 2009. Considering that synthetic cathinones are currently the second largest group of new psychoactive and dangerous substances among over 670 new psychoactive substances identified in Europe and monitored by the EMCDDA, research on them should be regarded as extremely important. This review focuses on the availability of synthetic cathinones on the illicit drug market, presentation of current trends in the use of these substances, and their mechanisms of action and toxicity. The authors discuss cases of intoxication with synthetic cathinones and post-mortem diagnostics as well as the problem of combined used of synthetic cathinones with other psychoactive substances. Literature as well as clinical and forensic data indicate the need for further research on the metabolism, toxicokinetics, toxicodynamics, clinical effects, and addictive potential of synthetic cathinones, especially in the context of potential threats caused by increased consumption of this group of drugs in future.

A two fatal cases of poisoning involving new cathinone derivative PV8.

α-Pyrrolidinoheptiophenone (PV8) is a representative of α-pyrrolidinophenone derivatives, a new group of synthetic cathinones. PV8 was first detected in illegal products in Japan in 2013. It is closely related to α-pyrrolidinovalerophenone (α-PVP), which was one of the most popular novel psychoactive substance (NPS) in Poland in years 2013-2015. The article presents two cases of fatal poisonings of 36-year-old man and 37-year-old woman, where a new cathinone derivative - PV8 was detected in biological material collected during medicolegal autopsies. The concentration of PV8, measured with LC-MS method, was in the first case - 0.26 µg/mL in blood and 0.11 µg/mL in urine and in the second - 0.07 µg/mL and 0.13 µg/mL, respectively. In both cases medicolegal experts finally have determined that the cause of death was fatal intoxication with the main role of PV8. This substance is another synthetic cathinone which is dangerous for live of the users and requires constant monitoring and further research.

Spectroscopic characterization and crystal structures of two cathinone derivatives: 1-(4-chlorophenyl)-2-(1-pyrrolidinyl)-pentan-1-one (4-chloro-α-PVP) sulfate and 1-(4-methylphenyl)-2-(dimethylamino)-propan-1-one (4-MDMC) hydrochloride salts, seized on illicit drug market.

PURPOSE: Two compounds newly found in the seizures by drug enforcement agencies were identified and characterized by various instrumental analytical methods. METHODS: The obtained powder samples were analyzed by gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometryn (LC-MSn), nuclear magnetic resonance (NMR) spectroscopy, infrared and Raman spectroscopy and X-ray crystallography. RESULTS: The two compounds were tentatively identified as 4-chloro-α-PVP and 4-MDMC by GC-MS, and LC-MS/MS. The confirmation of the results was made by NMR spectroscopy. The X-ray crystallography gave information that 4-chloro-α-PVP and 4-MDMC were in salted forms with sulfate and hydrochloride, respectively; in addition, both compounds existed as racemic mixtures. CONCLUSIONS: We could identify 4-chloro-α-PVP and 4-MDMC in the seizure powder samples by various analytical methods. X-ray crystallography was especially useful for identifying the salted forms and enantiomeric forms.

Spectroscopic characterization and crystal structures of two cathinone derivatives: N-ethyl-2-amino-1-phenylpropan-1-one (ethcathinone) hydrochloride and N-ethyl-2-amino-1-(4-chlorophenyl)propan-1-one (4-CEC) hydrochloride.

Comprehensive chemical characterization for two cathinone derivatives, N-ethyl-2-amino-1-phenylpropan-1-one (ethcathinone) hydrochloride and N-ethyl-2-amino-1-(4-chlorophenyl)-propan-1-one (4-chloroethcathinone, 4-CEC) hydrochloride, in material seized by drug enforcement agencies was performed by nuclear magnetic resonance (NMR) spectroscopy, infrared spectroscopy, gas chromatography-mass spectrometry in positive electron ionization mode, liquid chromatography-mass spectrometry in positive electrospray ionization mode and X-ray crystallography. The examined samples of these two compounds proved to be very pure for ethcathinone and mixed with very small quantities of other substances for 4-CEC by NMR spectroscopy and mass spectrometry. X-ray crystallographic studies confirmed the occurrence of both compounds as racemic mixtures. These spectroscopic and crystallographic data seem very useful for their identification. Especially for 4-CEC, this is the first description on its spectroscopic characterization in a scientific context to our knowledge.

Critical approach to flow injection gradient titration as a calibration method.

An attempt was made to demonstrate that flow injection gradient titration should not be considered as classical titration but rather as the indirect calibration method. This was shown experimentally by exploiting indirect spectrophotometric determination of chlorite ions in the presence of iron(II) in an acid environment with measurement of absorbance for the coloured Fe(II)/o-phenanthroline complex at 512nm. In such an analytical system, the peaks of a cut-off profile were obtained with two characteristic points corresponding to equivalent amounts of analyte and reagent, and peak widths were used as the analytical signal. The only difference between the approach presented and the classical flow injection titration procedure was not fundamental but of a technical nature and consisted in the fact that a sample loop of relatively great volume instead of a mixing chamber was installed into the flow injection system. The analytical performance of the developed calibration procedure is also presented and discussed.