In forensic toxicology, interpretation of postmortem (PM) drug concentrations might be complicated due to the lack of data concerning drug stability or PM redistribution (PMR). Regarding synthetic cannabinoids (SC), only sparse data are available, which derived from single case reports without any knowledge of dose and time of consumption. Thus, a controlled pig toxicokinetic study allowing for examination of PMR of SC was performed. Twelve pigs received a pulmonary dose of 200 µg/kg BW each of 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1pentyl-indole-3-yl)methanone (RCS-4), and Δ9-tetrahydrocannabinol via an ultrasonic nebulizer. Eight hours after, the pigs were put to death with T61 and specimens of relevant tissues and body fluids were collected. Subsequently, the animals were stored at room temperature (n = 6) or 4 °C (n = 6) and further samples were collected after 24, 48, and 72 h each. Concentrations were determined following enzymatic cleavage and solid-phase extraction by liquid-chromatography tandem mass spectrometry applying the standard addition approach. High concentrations of the parent compounds were observed in lung, liver, kidney and bile fluid/duodenum content as well as brain. HO-RCS-4 was the most prevalent metabolite detected in PM specimens. In general, changes of PM concentrations were found in every tissue and body fluid depending on the PM interval as well as storage temperature.
Nevertheless, regarding delivery efficiencies, the minor standard deviations indicate an acceptable reproducibility, suggesting that this administration system is suitable for application in TK studies.
Examining fatal poisonings, chronic exposure may be reflected by the concentration in tissues known for long-term storage of drugs. Δ9-tetrahydrocannabinol (THC) persists in adipose tissue (AT), but sparse data on synthetic cannabinoids (SC) are available. Thus, a controlled pig study evaluating antemortem (AM) disposition and postmortem (PM) concentration changes of the SC 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1-pentyl-indole-3-yl)methanone (RCS-4) as well as THC in AT was performed. The drugs were administered pulmonarily (200 µg/kg body weight) to twelve pigs. Subcutaneous (s.c.) AT specimens were collected after 15 and 30 min and then hourly up to 8 h. At the end, pigs were sacrificed and s.c., perirenal, and dorsal AT specimens were collected. The carcasses were stored at room temperature (RT; n = 6) or 4 °C (n = 6) and specimens were collected after 24, 48, and 72 h. After homogenization in acetonitrile and standard addition, LC–MS/MS was performed. Maximum concentrations were reached 0.5–2 h after administration amounting to 21 ± 13 ng/g (JWH-210), 24 ± 13 ng/g (RCS-4), and 22 ± 20 ng/g (THC) and stayed at a plateau level. Regarding the metabolites, very low concentrations of N-hydroxypentyl-RCS-4 (HO-RCS-4) were detected from 0.5 to 8 h. PM concentrations of parent compounds did not change significantly (p > 0.05) over time under both storage conditions. Concentrations of HO-RCS-4 significantly (p < 0.05) increased in perirenal AT during storage at RT. These results suggest a rapid distribution and persistence in s.c. AT. Furthermore, AT might be resistant to PM redistribution of parent compounds. However, significant PM increases of metabolite concentrations might be considered in perirenal AT.
In forensic case work, blood stain pattern analysis frequently aids in deducing the chain of actions or parts thereof taking place during an event leading to blood loss. Wiped single blood stains and/or groups of blood stains are seen at a majority of complex crime scenes. The appearance of wiped blood stains depends on droplet volume and stain age (as a function of blood viscosity and the degree of stain skeletonization) and characteristics of the stained surface (i.e., texture, temperature). Furthermore, based on the biochemical and biophysical properties of blood, not only the drying processes, but also complex coagulation cascades are relevant to the assessment of wiped blood stains. This study was designed to determine if anticoagulation therapies markedly affect the wipeability of blood stains over times elapsed since deposition and the overall drying process. A total of 813 blood stains, originating from donors being treated with acetylsalicylic acid (ASA), clopidogrel + ASA, low-molecular-weight heparin, or rivaroxaban, were dropped on common household tiles. Wipeability at an ambient temperature of 20 °C was tested for 22 time periods (1, 2, 3, 5, 10, 15…105 min since deposition). Whereas stains consisting of untreated blood were dried within 55 min, wipeability of all droplets originating from donors with prior anticoagulation treatment showed pronounced delays compared with the control, ranging from 20 min (ASA and clopidogrel + ASA) to 45 min (rivaroxaban). This pronounced effect was not seen in earlier studies, which might be explained by the higher volume of droplets used in this study, which resulted in a shift in relevance from drying to clotting processes. Significant differences between the drying times of the various anticoagulation regimes might be attributed to anticoagulant activity against different targets in the coagulation cascades. In conclusion, anticoagulation treatment prior to blood loss significantly affected the wipeability of blood stains. Anticoagulation therapy should therefore be taken into account in the analysis of blood stain patterns.
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