Are the (New) Synthetic Opioids U-47700, Tramadol and Their Main Metabolites Prone to Time-Dependent Postmortem Redistribution?—A Systematic Study Using an In Vivo Pig Model

Article

作者: Laschke, Matthias W ; Meyer, Markus R ; Potente, Stefan ; Schmidt, Peter H ; Walle, Nadja ; Nordmeier, Frederike ; Doerr, Adrian A ; Menger, Michael D ; Schaefer, Nadine

AbstractThe interpretation of analytical results in forensic postmortem (PM) cases often poses a great challenge, in particular, due to possible PM redistribution (PMR) phenomena. In terms of new synthetic opioids, such data are usually not available and, if so, they are from case reports without the exact knowledge of dose, user habits, time of consumption or PM interval (PMI). Hence, a controlled toxicokinetic pig study was performed allowing the examination of PM tissue distribution and possible PMR of U-47700, tramadol and the main metabolites N-desmethyl-U-47700 and O-desmethyltramadol (ODT). For this purpose, 12 domestic pigs received an intravenous dose of 100 µg/kg body weight (BW) U-47700 or 1,000 µg/kg BW tramadol, respectively. The animals were put to death with T61 8 h after administration, and relevant organs, tissues and body fluids were sampled. Subsequently, the animals were stored at room temperature (RT), and the samples were taken again after 24, 48, and 72 h PM. Following homogenization and solid-phase extraction, quantification was performed applying a standard addition approach and liquid chromatography–tandem mass spectrometry. Only low-to-moderate concentration changes of U-47700, tramadol and their main metabolites were found in the analyzed tissue specimens and body fluids during storage at RT depending on the chosen PMI. On the contrary, a remarkable concentration increase of tramadol was observed in the liver tissue. These findings indicate that both synthetic opioids and their main metabolites are only slightly prone to PMR and central blood might be the matrix of choice for quantification of these substances.

2022-05-20·Journal of Analytical Toxicology3区 · 医学

Perimortem Distribution of U-47700, Tramadol and Their Main Metabolites in Pigs Following Intravenous Administration

3区 · 医学

Article

作者: Laschke, Matthias W ; Meyer, Markus R ; Potente, Stefan ; Schmidt, Peter H ; Walle, Nadja ; Nordmeier, Frederike ; Doerr, Adrian A ; Menger, Michael D ; Schaefer, Nadine

AbstractIn spite of a decreasing number of new releases, new synthetic opioids (NSOs) are gaining increasing importance in postmortem (PM) forensic toxicology. For the interpretation of analytical results, toxicokinetic (TK) data, e.g., on tissue distribution, are helpful. Concerning NSOs, such data are usually not available due to the lack of controlled human studies. Hence, a controlled TK study using pigs was carried out, and the tissue distribution of U-47700 and tramadol as reference was examined. Twelve pigs received an intravenous dose of 100 µg/kg body weight (BW) U-47700 or 1,000 µg/kg BW tramadol. Eight hours after administration, the animals were put to death with T61. Relevant organs, body fluids and tissues were sampled. After homogenization and solid-phase extraction, quantification was performed applying standard addition and liquid chromatography--tandem mass spectrometry. At the time of death, the two parent compounds were determined in all analyzed specimens. Regarding U-47700, concentrations were highest in duodenum content, bile fluid and adipose tissue (AT). Concerning tramadol, next to bile fluid and duodenum content, highest concentrations were determined in the lung. Regarding the metabolites, N-desmethyl-U-47700 and O-desmethyltramadol (ODT) were detected in all analyzed specimens except for AT (ODT). Higher metabolite concentrations were found in specimens involved in metabolism. N-desmethyl-U-47700 showed much higher concentrations in routinely analyzed organs (lung, liver and kidney) than U-47700. To conclude, besides the routinely analyzed specimens in PM toxicology such as blood, urine or standard specimens like kidney or liver, AT, bile fluid and duodenum content could serve as alternative matrices. In case of U-47700, quantification of the main metabolite N-desmethyl-U-47700 is highly recommendable.

2021-04-01·The Canadian veterinary journal = La revue veterinaire canadienne

Evaluation of intravenous T-61 as a euthanasia method for birds.

Article

作者: Machin, Karen L ; Moritz, Antonietta L ; Zwueste, Danielle ; Schwean-Lardner, Karen ; Baker-Cook, Bethany I

The use of T-61 as a sole euthanasia agent for birds was investigated. Nine broiler chickens (Gallus gallus domesticus) were euthanized by intravenous T-61 and assessed for insensibility [brainstem reflexes: nictitating membrane reflex (NIC), palpebral blink reflex (PAL)], brain death [isoelectric electroencephalogram activity (EEG)], cessation of audible heartbeat, and abnormal electrocardiogram. Birds were considered dead when the heart rate was less than 180 beats/minute with an isoelectric EEG. No vocalization or wing flapping occurred. Both NIC and PAL were lost 10.5 s from start of injection and audible heartbeat ceased at 24.5 s. Latency to isoelectric activity was 16.6 s. All but 1 bird died within 60 s. Rapid induction of insensibility meant birds did not experience pain and distress within 10.5 s from start of injection and birds were not conscious during cardiac and circulatory arrest. Intravenous injection of T-61 is an effective and efficient euthanasia method for birds.

100 项与 T-61 相关的药物交易

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