Larabi Islam Amine, Joseph Delphine, Lesueur Camille, Alvarez Jean-Claude
Department of Pharmacology and Toxicology, Raymond Poincaré Hospital, AP-HP, 92380 Garches, France.
UVSQ, Université Paris-Saclay, Inserm U1018, CESP, Équipe MOODS, MasSpecLab, 78180 Montigny-le-Bretonneux, France.
Metabolites. 2023 Mar 16;13(3):432. doi: 10.3390/metabo13030432.
3-Hydroxyeticyclidine (3-HO-PCE) is a ketamine derivative that produces dissociative, hallucinogenic, and euphoric effects when consumed, but little is known about its pharmacological properties, metabolism, and toxicity compared to other designer ketamine analogs. To address this gap in knowledge, this study explored for the first time the metabolism of 3-HO-PCE. Based on this investigation, it is hypothesized that combining the use of Human Liver Microsomes (HLM) as an In vitro model with urine and hair samples from drug users may enable the identification of key analytes that can extend the detection window of 3-HO-PCE, particularly in cases of overdose. The analysis identified 15 putative metabolites, 12 of which are produced through phase I metabolism involving -dealkylation, deamination, and oxidation, and 3 through phase II -glucuronidation. The metabolism of 3-HO-PCE is similar to that of O-PCE, another designer ketamine of the eticyclidine family. The study identified M2a and hydroxy-PCA as reliable biomarkers for untargeted screening of the eticyclidine family in urine and hair, respectively. For targeted screening of 3-HO-PCE, M10 is recommended as the target analyte in urine, and M5 shows promise for long-term monitoring of 3-HO-PCE using hair analysis.
3-羟基乙环利定（3-HO-PCE）是一种氯胺酮衍生物，服用后会产生分离、致幻和欣快效果，但与其他合成氯胺酮类似物相比，其药理特性、代谢和毒性鲜为人知。为填补这一知识空白，本研究首次探索了3-HO-PCE的代谢情况。基于此项调查，推测将人肝微粒体（HLM）作为体外模型与吸毒者的尿液和毛发样本相结合，可能有助于识别关键分析物，从而延长3-HO-PCE的检测窗口，尤其是在过量用药的情况下。分析确定了15种推定代谢物，其中12种是通过涉及去烷基化、脱氨基和氧化的I相代谢产生的，3种是通过II相葡萄糖醛酸化产生的。3-HO-PCE的代谢与乙环利定家族的另一种合成氯胺酮O-PCE相似。该研究分别确定M2a和羟基-PCA为尿液和毛发中乙环利定家族非靶向筛查的可靠生物标志物。对于3-HO-PCE的靶向筛查，建议将M10作为尿液中的目标分析物，而M5有望用于通过毛发分析对3-HO-PCE进行长期监测。
