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AbstractMany neurodegenerative disorders and syndromes are associated with an excessive generation of reactive oxygen species (ROS) and oxidative stress. The pathways to nerve cell death induced by diverse potential neurotoxins such as peptides, excitatory amino acids, cytokines or synthetic drugs commonly share oxidative downstream processes, which can cause either an acute oxidative destruction or activate secondary events leading to apoptosis. The pathophysiological role of ROS has been intensively studied in in vitro and in vivo models of chronic neurodegenerative diseases such as Alzheimers disease (AD) and of syndromes associated with rapid nerve cell loss as occuring in stroke. In AD, oxidative neuronal cell dysfunction and cell death caused by protofibrils and aggregates of the ADassociated amyloid β protein (Aβ) may causally contribute to pathogenesis and progression. ROS and reactive nitrogen species also take part in the complex cascade of events and the detrimental effects occuring during ischemia and reperfusion in stroke. Direct antioxidants such as chainbreaking free radical scavengers can prevent oxidative nerve cell death. Although there is ample experimental evidence demonstrating neuroprotective activities of direct antioxidants in vitro, the clinical evidence for antioxidant compounds to act as protective drugs is relatively scarce. Here, the neuroprotective potential of antioxidant phenolic structures including αtocopherol (vitamin E) and 17βestradiol (estrogen) in vitro is summarized. In addition, the antioxidant and cytoprotective activities of lipophilic tyrosine and tryptophancontaining structures are discussed. Finally, an outlook is given on the neuroprotective potential of aromatic amines and imines, which may comprise novel lead structures for antioxidant drug design.

In 2012 benzodiazepine-type compounds started to extend the group of New Psychoactive Substances (NPS) sold on the internet as alleged legal recreational drugs. Initially, benzodiazepines like phenazepam and etizolam - which are still prescribed in some countries - were sold on the internet as recreational drugs. Subsequently, the group of so-called designer benzodiazepines was enlarged by compounds that either are active metabolites (e.g. norfludiazepam) or precursors (e.g. diclazepam) of known benzodiazepines or combine structural properties of different classical benzodiazepines (e.g. flubromazolam). Patents and scientific literature describe the synthesis and detailed results of animal model studies for more than a hundred different benzodiazepines, so it can be assumed that this sub-group of NPS will extend quickly in the future. The aim of this project was to develop an easy-to-use screening-method to detect and identify prescription and designer benzodiazepines and additionally obtain semi-quantitative information in a single run.

New synthetic cannabinoids (SC) frequently appear on the markets challenging toxicologists. Perceived as a legal alternative to cannabis a growing number of SCs is available. Consequently, analytical methods have to be adapted frequently to include newly emerging compounds. Since most SC are metabolized extensively metabolite identification prior to analyzing urine samples is inevitable. The presented study aimed at the development and implementation of a workflow allowing for the identification of the major in vitro phase I metabolites of new compounds by using dedicated software to mine analytical data of pooled human liver microsome (pHLM) incubations. The identified metabolites and their respective MSMS fragment information are utilized to update analytical methods for the reliable identification of SC uptake in human urine samples.

Hair analysis for drugs and drugs of abuse is increasingly applied in child protective cases. To estimate the potential risk to a child living in a household where drugs are consumed, not only the hair of the parents can be analyzed but also the hair of the child. In the case of hair analysis for cannabinoids the differentiation between external contamination and systemic uptake is particularly difficult, since the drug is quite often handled extensively prior to consumption (e.g. when preparing a joint) and smoke causes a further risk for an external contamination. As Δ9-tetrahydrocannabinolic acid A (THCA-A), the non-psychoactive biogenetic precursor of Δ9-tetrahydrocannabinol (THC), is not incorporated into the hair matrix through the bloodstream in relevant amounts it may act as a marker for external contamination.

If narcotics police officers or other persons handling drug material at work are suspected of consuming drugs, hair analysis may be used to prove or refute such suspicion. However, it is known for many drugs that differentiation of actual drug use from external contamination can be challenging or sometimes impossible. The aim of this study was to evaluate the extent of external contamination caused by handling of synthetic cannabinoid containing drug material under realistic conditions in a forensic laboratory.

As hair analysis is often used for abstinence control it is crucial to consider contamination by passive exposure, particularly when drugs are smoked. In this study, the composition of main-stream and side-stream smoke of herbal mixtures containing synthetic cannabinoids was investigated and put into the context of head hair concentrations of samples collected from individuals repeatedly exposed to side-stream smoke.