In the postmortem environment, some drugs and metabolites may degrade due to microbial activity, even forming degradation products that are not produced in humans. Consequently, underestimation or overestimation of perimortem drug concentrations or even false negatives are possible when analyzing postmortem specimens. Therefore, understanding whether medications may be susceptible to microbial degradation is critical in order to ensure that reliable detection and quantitation of drugs and their degradation products is achieved in toxicology screening methods. In this study, a “simulated postmortem blood” model constructed of antemortem human whole blood inoculated with a broad population of human fecal microorganisms was used to investigate the stability of 17 antidepressant and antipsychotic drugs. Microbial communities present in the experiments were determined to be relevant to postmortem blood microorganisms by 16S rRNA sequencing analyses. After 7 days of exposure to the community at 37°C, drug stability was evaluated using liquid chromatography coupled with diode array detection (LC‐DAD) and with quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS). Most of the investigated drugs were found to be stable in inoculated samples and noninoculated controls. However, the 1,2‐benzisothiazole antipsychotics, ziprasidone and lurasidone, were found to degrade at a rate comparable with the known labile control, risperidone. In longer experiments (7 to 12 months), where specimens were stored at −20°C, 4°C, and ambient temperature, N‐dealkylation degradation products were detected for many of the drugs, with greater formation in specimens stored at −20°C than at 4°C.
Inspired by nature’s ability to construct complex molecules through sequential synthetic transformations, we have developed an assembly line synthesis of α-aminophosphonates. In this approach, simple starting materials are continuously fed through a thin-film reactor where the intermediates accrue molecular complexity as they progress through the flow system. Flow chemistry allows rapid multi-step transformations to occur via reaction compartmentalization, an approach not amenable to using conventional flasks. Thin film processing can also access facile in situ solvent exchange to drive reaction efficiency, and through this method, α-aminophosphonate synthesis requires only 443 s residence time to produce 3.22 g h−1. Assembly line synthesis allows unprecedented reaction flexibility and processing efficiency.
Benzimidazole synthetic opioids are highly potent μ-opioid receptor agonists with heroin-like effects, including dose-dependent respiratory depression and a high risk of abuse and toxicity. Benzimidazoles were first detected in 2019 in Europe and Canada, with analytical confirmation of etodesnitazene, protonitazene and butonitazene in 2021. We report the first detections of these compounds in Australia, in two patients presenting with drug toxicity to Emergency Departments in the state of Victoria. Case 1 was a female in her 20s who rectally administered etodesnitazene and was found unconscious with a respiratory depression and hypotension. Case 2 was a female in her 30s who presented to the ED in a sedated state after taking a formulation of protonitazene which also contained butonitazene, in addition to methylamphetamine. She responded positively to naloxone. Novel synthetic opioids were used with prior experience of the formulations purchased, however the unpredictability of their effects was demonstrated by the acute toxicity experienced with this occasion of use. Toxicosurveillance of Emergency Department presentations with analytical confirmation of drugs is crucial in identifying emerging drugs in the community and informing harm reduction strategies.
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