The use of new psychoactive substances derived from ketamine is rarely reported in France. A chronic GHB, 3-MMC, and methoxetamine consumer presented a loss of consciousness in a chemsex context and was referred to the intensive care unit with a rapid and favorable outcome. To investigate the chemicals responsible for the intoxication, a comprehensive analysis was conducted on the ten plasma samples collected over a 29.5-hour period, urine obtained upon admission, a 2-cm hair strand sample, and a seized crystal. These analyses were performed using liquid chromatography hyphenated to high resolution tandem mass spectrometry operating in targeted and untargeted modes. Additionally, analyses using gas chromatography coupled to mass spectrometry and nuclear magnetic resonance were conducted to probe the composition of the seized crystal. The molecular network-based approach was employed for data processing in non-targeted analyses. It allowed to confirm a multidrug exposure encompassing GHB, methyl-(aminopropyl)benzofuran (MAPB), (aminopropyl)benzofuran (APB), methylmethcathinone, chloromethcathinone, and a new psychoactive substance belonging to the arylcyclohexylamine family namely deschloro-N-ethyl-ketamine (O-PCE). Molecular network analysis facilitated the annotation of 27 O-PCE metabolites, including phase II compounds not previously reported. Plasma kinetics of O-PCE allowed the estimation of the elimination half-life of ∼5 hours. Kinetics of O-PCE metabolites was additionally characterized, possibly useful as surrogate biomarkers of consumption. We also observed marked alterations in lipid metabolism related to poly consumption of drugs. In conclusion, this case report provides a comprehensive analysis of exposure to O-PCE in a multidrug user including kinetic and metabolism data in human.

中文翻译：

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毒代动力学和代谢相结合的方法来研究多种药物使用者的脱氯-N-乙基氯胺酮暴露情况

法国很少报道使用氯胺酮衍生的新型精神活性物质。一名长期服用 GHB、3-MMC 和甲氧西胺的患者在化学性行为中表现出意识丧失，并被转至重症监护室，并得到了快速且良好的结果。为了调查导致中毒的化学物质，对29.5小时内收集的10份血浆样本、入院时获得的尿液样本、2厘米发丝样本和检获的晶体进行了全面分析。这些分析是使用液相色谱与高分辨率串联质谱联用，以靶向和非靶向模式进行的。此外，还使用气相色谱法、质谱法和核磁共振进行分析，以探测所捕获晶体的成分。基于分子网络的方法用于非靶向分析中的数据处理。它可以确认多种药物暴露，包括 GHB、甲基-(氨丙基)苯并呋喃 (MAPB)、(氨丙基)苯并呋喃 (APB)、甲基甲卡西酮、氯甲卡西酮和属于芳基环己胺家族的新精神活性物质，即脱氯-N-乙基-氯胺酮（O-PCE）。分子网络分析促进了 27 种 O-PCE 代谢物的注释，包括以前未报道的 II 期化合物。 O-PCE 的血浆动力学可估计消除半衰期约为 5 小时。 O-PCE 代谢物的动力学也得到了表征，可能可用作消耗的替代生物标志物。我们还观察到与药物的多消耗相关的脂质代谢的显着变化。总之，本病例报告对多种药物使用者的 O-PCE 暴露情况进行了全面分析，包括人体动力学和代谢数据。