Piotr Adamowicz

Fatal Mephedrone Intoxication—A Case Report

A death caused by a new designer drug, 4-methylmethcathinone (mephedrone), is reported. Eight small plastic bags containing white powder were found in the jacket of a young dead male. Spot tests conducted by the police officer indicated the presence of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in the powders. Laboratory routine screening analyses of blood and vitreous humor did not reveal any positive results; therefore, 2C-B was excluded. Analysis of powders was conducted using gas chromatography-mass spectrometry and high-pressure liquid chromatography with diode array detection. The purity of mephedrone found in all powder samples was in the range of 80.4-87.3%. In connection with these findings, blood and vitreous humor samples were analyzed for mephedrone. Analyses were conducted using liquid chromatography-tandem mass spectrometry. Mephedrone was found in blood and vitreous humor at the concentrations of 5.5 and 7.1 µg/mL, respectively, revealing that this was a fatal mephedrone intoxication.

Analysis of UR-144 and its pyrolysis product in blood and their metabolites in urine.

UR-144 [(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone] is a synthetic cannabinoid, which has been detected in many herbal blends, resinous samples and powders seized from the Polish drug market since the beginning of 2012. This paper presents the case of intoxication by this substance. A complete picture of the symptoms observed by a witness, paramedics and medical doctors are given. In the analysis of powder residues from the plastic bag seized from the intoxicated person by gas chromatography-mass spectrometry (GC-MS), UR-144 and its major pyrolysis product [1-(1-pentyl-1H-indol-3-yl)-3-methyl-2-(propan-2-yl)but-3-en-1-one] were detected. Both substances were also identified in a blood sample collected on admission of the patient to hospital using liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS). Blood concentration of UR-144 was 6.1 ng/mL. A urine sample collected at the same time was analyzed by liquid chromatography-quadruple time-of-flight tandem mass spectrometry (LC-QTOF-MS). The parent substance and its pyrolysis products were not detected in urine, while their five metabolites were found. The experiments allowed the location of derivative groups to be established, and thus elucidate rough structures of the metabolites; a dihydroxylated metabolite of UR-144 and mono-, dihydroxylated and carboxylated metabolites of its pyrolysis product were identified.

Analysis of 4-MEC in biological and non-biological material—Three case reports

4-Methylethcathinone (4-MEC) is a designer drug that is structurally similar to mephedrone. This substance was identified in many drug seizures analyzed in the Institute of Forensic Research (IFR). This paper describes three of the first cases in which both powders and biological material were secured at the same time and delivered to the IFR for toxicological analysis. The first case concerned a man who died in a car crash. The second case describes a death associated with multiple-drug intake, including 4-MEC. In this case, however, the death was the result of an overdose of para-methoxyamphetamine (PMA). In the third case, the man was arrested for possession of illicit drugs. Analysis of powders was carried out using gas chromatography-mass spectrometry (GC-MS) and high pressure liquid chromatography with diode array detection (HPLC-DAD). The purity of 4-MEC found in powder samples was 51% and 78%. Analyses of biological material were carried out using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 4-MEC was found in blood samples at concentrations of 46, 56 and 152 ng/mL.

Fatal intoxication with 3-methyl-N-methylcathinone (3-MMC) and 5-(2-aminopropyl)benzofuran (5-APB)

The emergence of a large number of new psychoactive substances (NPSs) in recent years poses a serious problem to clinical and forensic toxicologists. Here we report a patient who administrated ca. 500mg of 3-MMC (3-methyl-N-methylcathinone) and 400mg of 5-APB (5-(2-aminopropyl)benzofuran) in combination with 80g of ethyl alcohol. The clinical manifestations included agitation, seizures, hypertension, tachycardia, hyperthermia and bradycardia. The patient did not recover and died around 4h after the use of drugs. The cause of death was acute cardiovascular collapse that occurred following mixed intoxication with NPSs and alcohol. Toxicological analysis of post-mortem blood revealed 3-MMC and 5-APB in concentrations of 1.6μg/mL and 5.6μg/mL, respectively. Moreover, the serum alcohol concentration was 1.4g/L in ante-mortem sample collected 1h after admission to the hospital. This is the first report on blood concentration of 3-MMC and 5-APB in fatal intoxication.

Detection of buphedrone in biological and non-biological material – Two case reports

Buphedrone (2-(methylamino)-1-phenylbutan-1-one, α-methylamino-butyrophenone, MABP) is a positional isomer of mephedrone. In Poland, it was marketed in the second half of 2010 after the banning of mephedrone. Buphedrone is a stimulant that is snorted, smoked or taken orally. This substance was identified in 15 products seized by law enforcement after August 2010 and analysed in the Institute of Forensic Research (IFR). Buphedrone was the sole psychoactive substance in only 5 products. It was mixed mainly with 4-MEC and MDPV. This paper presents two cases in which both biological and non-biological materials were delivered to the IFR for toxicological analysis. In the first case, a passenger car crashed into a truck. The car driver suffered severe injuries resulting in his death. During external inspection of the deceased the police discovered several packages containing a white powder. In the second case, a man was arrested for possession of illicit drugs. Analysis of powders was carried out using gas chromatography-mass spectrometry (GC-MS) and high-pressure liquid chromatography with diode array detection (HPLC-DAD). The purity of buphedrone found in powder samples was in the range of 58-68%. Analyses of blood were carried out using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Buphedrone was found in the blood of the deceased at a concentration of 127 ng/mL and of the drug user/seller at 3 ng/mL.

Fatal Intoxication with Methoxetamine

Methoxetamine (MXE) is a new synthetic drug of abuse structurally related to ketamine and phencyclidine. A case of a 29‐year‐old male with acute toxicity related to the analytically confirmed use of MXE is reported. The man was found dead at his residence. Biological material was analyzed using liquid chromatography–tandem mass spectrometry. The concentration of MXE in urine of the deceased was 85 μg/mL. Despite the vial containing the blood sample being destroyed during transportation and the blood leaking out into the cardboard packaging, the blood level of MXE was estimated. After determination of the cardboard grammage (approx. 400 g/m3) and the mean mass of the blood obtained after drying (0.1785 ± 0.0173 g per 1 mL), the estimated blood concentration of MXE was found to be 5.8 μg/mL. The high concentration of MXE in blood and urine and the circumstances of the case indicate an unintentional, fatal intoxication with this substance.

Acute intoxication of four individuals following use of the synthetic cannabinoid MAB-CHMINACA

Abstract Context: The largest group of new psychoactive substances (NPS) are synthetic cannabinoids (SC). Those that become controlled are immediately replaced by new uncontrolled substances. The recent resurgence of the NPS market in Poland resulted in a further amendment to the Drug Addiction Counteraction Act. This resulted in significant changes in the composition of “legal high” preparations, and consequently a large outbreak of intoxications with SC was reported in Poland at the beginning of July 2015. Case details: This paper describes the circumstances of intoxication and toxicological findings in an acute intoxication of four individuals with MAB-CHMINACA. They each smoked tobacco mixed with powder from the package with the description “AM-2201”. The adverse effects observed in the individuals included vomiting, seizures, limb twisting, muscle tremors, aggression, agitation, slurred speech, blood pressure spikes, wheezing, respiratory failure and losses of consciousness. Blood samples were analysed using liquid chromatography with mass spectrometry. Results from analysis performed on the blood samples showed the presence of MAB-CHMINACA, while AM-2201 was not found (LOD 0.09 ng/mL). The determined concentrations were 5.2, 1.3, 1.7 and 14.6 ng/mL, respectively. The analyses of the blood did not reveal any other substances (excluding medicines given in hospital). Conclusion: The presented cases show the health risks associated with MAB-CHMINACA use and confirm that “legal high” preparations do not always contain a substance represented on the package.

3-Methylmethcathinone--Interpretation of Blood Concentrations Based on Analysis of 95 Cases.

3-Methylmethcathinone (3-MMC) has been one of the most popular new psychoactive substances (NPS) in Poland in recent years. 3-MMC was found in blood in 95 cases sent to the Institute of Forensic Research (IFR) during the two and a half year period, from 2013 to half of 2015. 3-MMC was determined in 13 and 48 cases in 2013 and 2014 year-round casework, respectively, while only in the first half of 2015 year it was present in 34 cases. In most cases, 3-MMC was detected together with other novel psychoactive substances and conventional drugs. Blood analyses for 3-MMC were carried out using liquid chromatography-tandem mass spectrometry (LC-MS-MS). The concentrations of 3-MMC in all 95 cases were in the range from traces (<1 ng/mL) up to 1.6 µg/mL (mean concentration 51.3 ng/mL, median 18.5 ng/mL). Concentration ranges in particular types of cases were respectively: DUID cases: 1-171 ng/mL; traffic accidents: <1-29 ng/mL; drug possession: 2-408 ng/mL; intoxication: <1-1600 ng/mL and other: <1-61 ng/mL. The parameters of the developed method such as the LOD (0.02 ng/mL) and LOQ (1 ng/mL) demonstrate that the method is well suited for the analysis of blood samples for 3-MMC and covers the range of typical blood concentrations.

Distinction of constitutional isomers of mephedrone by chromatographic and spectrometric methods

Many new psychoactive substances (NPS) have similar chemical structures. Separation and unequivocal identification of structural isomers is an important issue due to the fact that they can differ in pharmacology, toxicology, effects and action on the human body, as well as legal status. This paper is aimed at comparing the abilities of different analytical methods (GC-MS, UHPLC-DAD, LC-MS/MS), to distinguish mephedrone and its isomers: 3-MMC, 2-MMC, buphedrone, metamfepramone and ethcathinone. These techniques allowed for distinction between the isomers of mephedrone. In the GC-MS method, combining retention times with the mass spectra made the differentiation efficient. In the UHPLC-DAD conditions, it was impossible to distinguish the isomers based on their retention times, but the UV/VIS spectra were useful in identification. The separation conditions were optimised for the LC-MS/MS method. The identification of isomers was supported by the different intensity of product ions. The LODs for the GC-MS method (1000–2500 ng/mL) in scan mode were definitely the worst. The values for the UHPLC-DAD method were much better (1.4–2.7 ng/mL) making this assay suitable for the analysis of biological material. The LC-MS/MS method was sensitive enough (LODs = 0.03–0.39 ng/mL) for the analysis of biological material even a long time after the initial drug use.

Acidity of substituted cathinones studied by capillary electrophoresis using the standard and fast alternative approaches

Cathinone derivatives are notorious but still weakly characterized molecules, known mainly as components of the designer and illicit drugs. The knowledge on their acidity is scarce and incomplete, therefore, we decided to determine the pKa values for six of them: 2-methylmethcathinone, 3-methylmethcathinone, 4-methylmethcathinone, α-pyrrolidinovalerophenone, methylenedioxypyrovalerone and ephedrone. For that purpose we employed capillary electrophoresis, which is known for its accurateness in comparison to other analytical techniques. We used and compared two methodologically different approaches. The standard method relied on measuring electrophoretic mobility across the broad pH range and fitting the sigmoidal function. The obtained pKa values were in the range 8.59-9.10, thus these molecules remain mostly protonated and positively ionized in the physiological conditions. The alternative two-values (TVM) and one-value methods (OVM), proposed by us previously, have been used herein for the first time to the cationic molecules. TVM enables estimation of pKa using only two electrophoretic mobility values, referring to the total and partial ionization. OVM requires only a single measurement because mobility of ion is predicted theoretically. Both TVM and OVM yielded only a small deviation of pKa from the standard approach, averagely 0.07-0.09pH unit. Two important issues have also been addressed: the potential of a maximally fast calculation method using no repetition at the given pH, and the accuracy of method with regard to pH attributed to partial ionization. As a whole, the analytical potential of the TVM/OVM approach seems to be huge and invaluable for fast pKa screening/estimation.