Session: New Aspects of Clinical & Forensic Toxicology

Session Chair: Prof. Dr. Hans Maurer, Dr. Dirk K. Wissenbach
The GTFCh certified the following sessions with two points each: • New Aspects of Clinical & Forensic Toxicology (22.06.2022; ICM/Hall 5; 9:30-11:30 a.m.) • Rules for Mass Spectrometry Applications (22.06.2022; ICM/Hall 5; 12:30-2:30 p.m.) • New Psychoactive Substances – Still a Topic in Forensic Research? (22.06.2022; ICM/Hall 5; 3:00-5:00 p.m.) In order to collect the certification points for one or more sessions after the event (valid for the GTFCh training programs: Forensic Toxicologist, Forensic Chemist, Clinical Toxicologist, and Forensic-Clinical Chemist), please make sure to sign the respective attendance list, to be circulated during each of the sessions. ;
English

Possibilities and limitations of metabolomics research in clinical and forensic toxicology

Dr. Sven Baumann, Uni Leipzig
Metabolomics characterizes the analysis of endo- and exogenous metabolites (small molecules with <1000 Da molecular weight) in an organism and investigates the bottom of the “omics” cascade preceded by gen-, transcript-, and proteomics. The metabolome is related to the phenotype and is the most dynamic “ome” including top-down input as well as from environmental factors e.g. lifestyle, environmental stressors or xenobiotic substances. Metabolome studies target the qualitative and quantitative characterization of analytes with changes appearing in the investigated system in response to a certain stimulus. Besides targeted metabolomics triggering preselected analytes or substance classes (suspect target screening) in untargeted so called global or comprehensive metabolomic approaches “the whole metabolome” will be covered, which is, due to the chemical diversity of the metabolites, rather impossible. The use of metabolomic strategies in clinical and/or forensic toxicology is often the alternative option when conventional quantitative methods show a lack in the detectability of the substances of interest or additional information is needed. The connection to metabolomic screenings enables the search for indirect biomarkers indicating previous drug consumption. This could be helpful to prolong a limited analytical detection window e.g. in the determination of gamma-hydroxybutyric acid. It could also help to survey a complex analytical scenario like the identification of unknown sub- and parent structures or the mode of actions of new psychoactive substances. Further on, metabolomic studies showed their value in abstinence control drug testing scenarios to unravel illicit sample adulteration or manipulation of urine or hair specimen. In postmortem toxicology metabolomics might address issues of postmortem redistribution and complement traditional methods for the estimation of the postmortem interval. To perform a valid and reproducible metabolomic screening lots of biological confounders e.g. nutrition, co-medication, lifestyle has to be taken into account. Further on, the effectiveness of metabolomics desperately depends on pre-analytical sampling factors and standardization of material, collection, storage, and handling. Especially in forensic toxicology the sample material is often versatile which increases the risk of triggering sample inherent variations. Moreover reliable and robust analytical methods connected to traceable and reproducible data processing tools as well as an unambiguous identification of potential targets by validation using reference substances are necessary to avoid black box phenomena and the production of bioinformatic garbage. Additionally, metabolomics findings have to be verified via pathway analyses in systems biological approaches to unravel underlying mechanisms and ensure the truth of the acquired data.
22-Jun-2022 09:30 (40 Minutes) ICM/Hall 5
English

Progress on testing for sample adulteration

Dr. Andrea Steuer, Universität Zürich
Drug testing in order to prove abstinence of ethanol, drugs of abuse (DOA) or highly addictive prescription drugs e.g. in the context of regaining driver’s license or workplace drug testing is well established and accepted all over the world. Urine thereby still represents one of the matrices of choice givenits ease of collection and itsrelatively wide window of detection for most drugs and/or drug metabolites. Additionally, hair analysis gained major interest being collectable non-invasive, easyto storeand due to its long-term detection windowof even several months. To avoid positive drug testing, different adulterationstrategiesare described: substitution, e.g.withartificial urine,dilution or washing out of DOAs in urine or hair, respectively, andchemical adulteration, usually by oxidative treatment. In this context, reliable detection of differentsampleadulterationattempts represents a critical step for laboratories in abstinence control settings.The current presentation will provide an overview of currently available parameters to obtain evidencefor manipulation of urine or hair samples and beyond that focus on new advances or strategies for sample adulteration detection, e.g. through metabolome approaches. In order to test for all known adulterants several methods would be necessary, which most often is neither time-nor cost-effective.Creatinineis a suitable, routinely used marker for urine dilution. Integrity testing, spot and dipstick tests or integrated sample checks to commercially available immunoassay systems are often performed as a time –and cost-effective methodto test for urine adulteration in general butare also associated with high rates of false positives or false negatives. In hair analysis, visual inspection of hair samples and colored extracts may cause suspicionof (cosmetic)hair treatments. Workflows employing liquid chromatography (LC) or gas chromatography (GC) –mass spectrometry (MS)techniquesmore specificallyfocused on the detection of typical oxidation products of DOAsto prove their consumption despite a chemical adulteration attempt. Independent of the DOA consumed, new metabolome approaches tried to use the presence or absence of endogenous compounds as indicators for sample manipulation, e.g. an artificial urine sample. In case of oxidative treatments, specific oxidation products of matrix constituents, e.g. the melanin degradation products 1H-pyrrole-2,3,5-tricarboxylic acid (PTCA)or 1H-pyrrole-2,3,4,5-tetracarboxylic acid (PTeCA)in hair samples, mightrepresent valuable markers for sample manipulation.
22-Jun-2022 10:10 (40 Minutes) ICM/Hall 5
English

Cytotoxicity testing – a task also in clinical & forensic toxicology?

Prof. Dr. Markus R. Meyer, Universität des Saarlandes
In vitro cytotoxicity testing is crucial and mandatory in therapeutic drug development. This is not the case for non-therapeutic compounds such as drugs of abuse or – how they are called nowadays – new psychoactive substances. Numerous case reports of intoxications or even deaths after intake of such compounds demonstrate their threat on public health. [1] Some reports associated their intake with liver failure, [2] but detailed knowledge about certain cytotoxicity is usually unknown. To reveal such a potential is thus one task in the field of (analytical) toxicology. The knowledge can in turn help to explain outcomes of chronic intake, symptoms in overdose cases, or fatal events associated with new psychoactive substances abuse. Recent studies investigated single cytotoxicity biomarkers in individual experiments such as cell viability, leakage of lactate dehydrogenase or cell death. [3] To gain a deeper insight into intracellular processes, it may be favorable to monitor multiple parameters using high-content screening assays. [4] The talk will present, summarize, and discuss published studies and strategies related to the cytotoxic potential of non-therapeutic compounds, particularly new psychoactive substances.
22-Jun-2022 10:50 (40 Minutes) ICM/Hall 5