1,721,040 research outputs found

    Toxicological Investigation of a Case Series Involving the Synthetic Cathinone α-Pyrrolidinohexiophenone (α-PHP) and Identification of Phase I and II Metabolites in Human Urine

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    Abstract α-Pyrrolidinohexiophenone (α-PHP) is a derivative of the class of α-pyrrolidinophenones, a subgroup of synthetic cathinones. These substances are the second most abused drugs of new psychoactive substances. Here, we report the toxicological investigation of a series of 29 authentic forensic and clinical cases with analytically confirmed intake of α-PHP including two cases of drug testing in newborns using meconium. The age range of subjects where serum samples were available was 23–51 years (median 39.5), and 90% were male. Serum α-PHP concentrations, determined by a validated LC–MS-MS method, showed a high variability ranging from 1 to 83 ng/mL (mean, 40 ng/mL; median, 36 ng/mL). Comprehensive toxicological analysis revealed co-consumption of other psychotropic drugs in almost all cases with frequent occurrence of opiates (60%), benzodiazepines (35%), cannabinoids (30%), and cocaine (20%). Hence, forensic and clinical symptoms like aggressive behavior, sweating, delayed physical response, and impaired balance could not be explained by the abuse of α-PHP alone but rather by poly-intoxications. Liquid chromatography-quadrupole time-of-flight mass spectrometry and gas chromatography-mass spectrometry were used to investigate the metabolism of α-PHP in vivo using authentic human urine samples. Altogether, 11 phase I metabolites and 5 phase II glucuronides could be identified by this approach. Apart from the parent drug, most abundant findings in urine were the metabolites dihydroxy-pyrrolidinyl-α-PHP and dihydro-α-PHP and, to a lesser extent, 2ʹ-oxo-dihydro-α-PHP and 2ʹ-oxo-α-PHP. Monitoring of these metabolites along with the parent drug in forensic and clinical toxicology could unambiguously prove the abuse of the novel designer drug α-PHP.</jats:p

    Intoxication cases associated with the novel designer drug 3′,4′‐methylenedioxy‐α‐pyrrolidinohexanophenone and studies on its human metabolism using high‐resolution mass spectrometry

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    Abstract Among the increasing number of new psychoactive substances, 3′,4′‐methylenedioxy‐α‐pyrrolidinohexanophenone (MDPHP) belongs to the group of synthetic cathinones, which are the derivatives of the naturally occurring compound cathinone, the main psychoactive ingredient in the khat plant. Currently, only limited data are available for MDPHP, and no information is available on its human metabolism. We describe the toxicological investigation of nine cases associated with the use of MDPHP during the period February–June 2019. Serum MDPHP concentrations showed a high variability ranging from 3.3 to 140 ng/mL (mean 30.3 ng/mL and median 16 ng/mL). Intoxication symptoms of the described cases could not be explained by the abuse of MDPHP alone because in all cases the co‐consumption of other psychotropic drugs with frequent occurrence of opiates and benzodiazepines could be verified. Therefore, the patients showed different clinical symptoms, including aggressive behaviour, delayed physical response, loss of consciousness and coma. Liquid chromatography–high‐resolution mass spectrometry was successfully used to investigate the human in vivo metabolism of MDPHP using authentic human urine samples. The metabolism data for MDPHP were further substantiated by the analysis of human urine using gas chromatography–mass spectrometry (GC–MS, a widely used systematic toxicological analysis method appropriate for the toxicological detection of MDPHP intake), which revealed the presence of seven phase I metabolites and three phase II metabolites as glucuronides. GC‐MS spectral data for MDPHP and metabolites are provided. The identified metabolite pattern corroborates the principal metabolic pathways of α‐pyrrolidinophenones in humans.In this study, we describe the toxicological investigation of nine cases associated with the use of the novel designer stimulant MDPHP. Serum concentrations, analytically confirmed co‐consumption, and intoxication symptoms are discussed. High‐resolution mass spectrometry and gas chromatography–mass spectrometry was successfully used to investigate the human in vivo metabolism of MDPHP using authentic human urine samples. The identified metabolite pattern, including seven phase I metabolites and three glucuronides, corroborates the principal metabolic pathways of α‐pyrrolidinophenones in humans. imag

    Synthetic cannabinoids in hair—Prevalence of use in abstinence control programs for driver's license regranting in Germany

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    Although the use, structural variety, and prevalence of synthetic cannabinoids (SCs) have steadily increased on the drug market, they are rarely analyzed in abstinence control programs for driver's license regranting. The aim of this study was to determine the SC prevalence in these programs by analyzing hair samples collected between March 2020 and March 2021 from various regions in Germany, mainly Bavaria (40%). Specimens were analyzed quantitatively for drugs of abuse and qualitatively for 107 SCs. Hair samples were screened by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and to search for unknown SC analogs, positive samples were additionally screened by liquid chromatography-high resolution time of flight mass spectrometry (LC-qTOF/MS). The analysis of 5097 hair samples resulted in 181 SC detections (3.6%), showing a wide range of 44 SCs, with up to 13 different compounds found in a single sample. The most prevalent compounds were 5F-MDMB-PICA and MDMB-4en-PINACA; furthermore, 10 new substances not initially covered by LC-MS/MS analysis were detected by LC-qTOF/MS. The SC positivity rate was comparable to cocaine (5.4%) and amphetamine (2.6%). Only in 35 cases (0.7%), SC analysis was requested by the clients, highlighting the insufficient coverage of SC consumption in the studied collective. In summary, hair sample analysis proved to be a valuable tool to monitor the use of SCs. In order to keep pace with newly emerging SC analogs, an up-to-date analytical method is essential. Prospectively, SCs should be more routinely screened in hair analysis for abstinence control to avoid cannabis substitution by SCs.Synthetic cannabinoids (SCs) have steadily increased on the drug market but are rarely analyzed in abstinence control programs for driver's license regranting. Between March 2020 and March 2021, hair samples from this collective were retrospectively screened for SCs by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and those testing positive were additionally screened by liquid chromatography-high resolution time of flight mass spectrometry (LC-qTOF/MS).imag

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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