The use of new psychoactive substances (NPS) has rapidly increased over the last decade. In the last 4 years, producers increasingly appear to be targeting non-controlled synthetic opioids, involving fentanyl derivatives such as ocfentanil (OcF). Identification of metabolites is of major importance in the context of NPS use, as it could improve the detection window in biological matrices in clinical and forensic intoxication cases. Hence, this work aims to report a fatality involving OcF documented by the identification of metabolites. A 30-year-old woman was found dead at home: an unidentified powder was found near her body and some injection sites were found at the autopsy. Toxicological analyses allowed to determine the presence of OcF in the powder, blood (3.7/3.9 μg/L, peripheral/cardiac) and in other post-mortem samples. The most relevant potential CYP- and UGT-dependent metabolites of OcF were investigated in vitro using human liver microsome incubation and liquid chromatography coupled with high resolution mass spectrometry, and subsequently confirmed in post-mortem samples. Four OcF metabolites were produced in vitro (a mono-hydroxylated OcF, O-desmethylOcF, a hydroxylated desmethylOcF and a glucuronidated form of the O-desmethylOcF), and all except the glucuronide were observed in blood and bile post-mortem samples. Considering the relative intensity of the chromatographic peak areas, O-desmethylOcF can be suggested to be an abundant metabolite of OcF. Nevertheless, the relevance of O-desmethylOcF as being a complementary analytical target of OcF for OcF use detection needs further in vivo confirmation, especially through analysis of urines from users.
The analysis of hair to detect drugs and drugs of abuse is performed in various contexts, including child protection cases, abstinence control programs, and workplace drug testing. This alternative matrix offers several advantages, such as a large detection window (months) and non-invasive collection. Segmental analysis of multiple hair strands for drugs and metabolites has been widely reported in the literature over the past three decades, whereas a review of the literature showed that there are only 26 articles that report the analysis of a single hair. They focus on two approaches: mass spectrometry imaging techniques, which improve the resolution of dating an intoxication or conventional methods, such as gas chromatography mass spectrometry and liquid chromatography tandem mass spectrometry (LC-MS/MS). Improved sensitivity of LC-MS/MS techniques allows the evaluation of drug content in segments of a single hair. However, the units used to express the results vary, and depend on the authors. Following a review of the literature, we present a case that illustrates drug analyses both in a strand of hair and a single hair. In this case of exposure of a child to zuclopenthixol (ZPT), the analysis of ZPT in a single segmented hair by LC-MS/MS strengthened the presumption of a single administration.
Aims. 3,5,4′-Trihydroxy-trans-stilbene, a natural polyphenolic compound present in wine and grapes and better known as resveratrol, has free radical scavenging properties and is a potent protector against oxidative stress induced by alcohol metabolism. Today, the mechanism by which ethanol exerts its toxicity is still not well understood, but it is generally considered that free radical generation plays an important role in the appearance of structural and functional alterations in cells. The aim of this study was to evaluate the protective action of resveratrol against ethanol-induced brain cell injury. Methods. Primary cultures of rat astrocytes were exposed to ethanol, with or without a pretreatment with resveratrol. We examined the dose-dependent effects of this resveratrol pretreatment on cytotoxicity and genotoxicity induced by ethanol. Cytotoxicity was assessed using the MTT reduction test. Genotoxicity was evidenced using single cell gel electrophoresis. In addition, DNA staining with fluorescent dyes allowed visualization of nuclear damage using confocal microscopy. Results. Cell pretreatment with low concentrations of trans-resveratrol (0.1–10 μM) slowed down cell death and DNA damage induced by ethanol exposure, while higher concentrations (50–100 μM) enhanced these same effects. No protection by cis-resveratrol was observed. Conclusion. Protection offered by trans-resveratrol against ethanol-induced neurotoxicity was only effective for low concentrations of this polyphenol.
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