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

Abstract

The 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-desmethylU-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.