Entwicklung einer vollautomatisierten massenspektrometrischen Methode zum Nachweis von Neuen Psychoaktiven Substanzen in Körperflüssigkeiten und deren Anwendung auf forensisch-toxikologische Fragestellungen

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As of the end of 2018 the EU Early Warning System of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) was monitoring more than 730 new psychoactive substances (NPS). From 2005 onwards, with the increasing emergence of NPS and the accompanying diversity and swift development drug market, forensic toxicology and clinical chemistry faced major challenges with regard to the analytical detectability and interpretation of analysis results. Robust and sensitive analytical methods for the qualitative and quantitative determination of NPS in biological matrices were therefore needed in order to reveal NPS intoxication and substance abuse in abstinence and doping checks, or to evaluate the degree of influence at a specific time of incident or time of death. The first part of this work describes the development of a fully automated in-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (in-line SPE-LC-MS/MS) method for the determination of 95 synthetic stimulants in serum. This method was validated according to forensic-toxicological guidelines and was tested by application to samples where there was suspicion of drug influence. Seven out of the 28 samples were determined positive for NPS consumption. The method was successfully incorporated into routine analytical procedures at the Institute of Legal Medicine, Faculty of Medicine, at the University of Cologne, and is continuously updated by inclusion of new analytes. The second part of this work centres on the prevalence of NPS stimulant use, and its relevance as cause of death amongst individuals in the greater Cologne area. For that purpose, the method described in the first part of this work was optimized and validated according to the forensic-toxicological guidelines for application in urine. On behalf of public prosecutors, in the period between January 2011 and May 2017, urine-specimens (or, in cases where urine was not available, kidney tissue) from 268 young (≤ 35 years) deceased individuals were systematically investigated with regards to stimulants, especially NPS. A total of 17 cases (6%) were tested positive for NPS. A subsequent investigation of blood samples (if available) of the deceased with positive NPS urine results showed that, NPS could be assigned as the leading cause of death, or of toxicological relevance, in the cause of death in five cases. In two cases, NPS was judged to be a component of a multidrug poisoning, but of minor relevance. The third part of the work describes an organ-distribution investigation, which was carried out on two deceased who consumed methylenedioxypyrovalerone (MDPV), α-pyrrolidinopentiophenone (α-PVP), methoxetamine (MXE) and 4-methylethcathinone (4-MEC). In this context, two different extraction methods were compared with each other – a QuEChERS (acronym for quick, easy, cheap, effective, rugged and safe) approach and an automated solid phase extraction – comparisons focused on the “swiftness” (speed of analysis), easiness (ease of use), efficacy and safety. Both techniques were suitable for the extraction of NPS at low concentrations in body fluids and tissues. The SPE method was more environmentally friendly (low consumption of solvents) with advantages such as rapidity and automation. Almost no matrix effects and sufficient recoveries (>50%) were observed on the analytes of interest (MDPV, α-PVP, MXE and 4-MEC) when analyzed by LC–MS/MS with the QuEChERS method. The results suggest that the QuEChERS approach could be an attractive alternative method for organ preparations in forensic casework. Especially due to the limited data, the insights gained into the post-mortem distribution of MDPV, MXE, 4-MEC and α-PVP will be of considerable value for the future assessment of fatal intoxications involving the aforementioned substances. The fourth and last part of this work centres on the investigation surrounding a fatality of a young man, particularly the organ distribution and post-mortem redistribution (including determination of the heart blood/peripheral blood) ratio of the designer stimulant 3-fluorophenmetrazine (3-FPM) and the benzodiazepines pyrazolam as well as diclazepam and it’s metabolites delorazepam, lorazepam, and lormetazepam. As knowledge of post-mortem concentrations and redistribution effects of NPS is limited, the results will be beneficial in expanding the current knowledge of these NPS.
Original languageGerman
Place of PublicationKöln
PublisherDeutsche Sporthochschule Köln
Number of pages41
Publication statusPublished - 2020

ID: 5291870


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