Mestria Serena, Odoardi Sara, Valentini Valeria, Corli Giorgia, Bassi Marta, Marti Matteo, Strano-Rossi Sabina
Department of Health Surveillance and Bioethics, Forensic Toxicology Laboratory, Università Cattolica del Sacro Cuore F. Policlinico Gemelli IRCCS, Rome, Italy.
Department of Translational Medicine, Section of Legal Medicine, LTTA Center and University Center of Gender Medicine, University of Ferrara, Ferrara, Italy.
Drug Test Anal. 2025 Jun;17(6):772-778. doi: 10.1002/dta.3782. Epub 2024 Jul 31.
The metabolism of 3-chloromethcathinone (3-CMC) was studied after controlled administration in a murine model using the dried blood spot (DBS) technique for the sampling, storage and purification of blood samples. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) was used for the identification of metabolites and investigation of their fragmentation pattern. Subsequently, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for their identification and 3-CMC quantification in routine workload. The main metabolites identified were two stereoisomers of dihydro-CMC, N-demethyl-CMC, and dihydro-N-demethyl-CMC. The stability of 3-CMC and of its metabolites deposited on DBS was evaluated by replicate analyses after 30, 50, and 90 days, demonstrating a decrease in concentration. It was more pronounced for 3-CMC, with -67% and -82% percentage deviation from the initial concentrations, and for N-demethyl 3-CMC (decrease comprised between -48% and -88%) than for the di-hydro metabolites, ranging from -5% to -37%. Regardless, all of them were detectable till 90 days after deposition as DBS. The possibility of identifying 3-CMC and its metabolites with high sensitivity is an invaluable tool for the diagnosis of exposure to the substance, also in low doses or after some hours, and for various applications in clinical and forensic toxicology, such as driving under the influence, drug-facilitated crimes, and addiction to intoxications. DBS demonstrated to be a reliable technique for the sampling, storage, and purification of the blood specimen for 3-CMC and metabolite detection.
在小鼠模型中，采用干血斑（DBS）技术对血液样本进行采样、储存和纯化后，对3-氯甲基卡西酮（3-CMC）的代谢情况进行了研究。液相色谱-高分辨率质谱（LC-HRMS）用于鉴定代谢产物并研究其碎裂模式。随后，开发了一种液相色谱-串联质谱（LC-MS/MS）方法，用于常规工作量下代谢产物的鉴定和3-CMC的定量分析。鉴定出的主要代谢产物为二氢-CMC的两种立体异构体、N-去甲基-CMC和二氢-N-去甲基-CMC。通过在30、50和90天后进行重复分析，评估了沉积在DBS上的3-CMC及其代谢产物的稳定性，结果表明浓度有所下降。3-CMC的浓度下降更为明显，与初始浓度相比，偏差百分比分别为-67%和-82%，N-去甲基3-CMC的浓度下降幅度在-48%至-88%之间，而二氢代谢产物的浓度下降幅度在-5%至-37%之间。无论如何，在沉积为DBS后的90天内，所有这些代谢产物均可检测到。高灵敏度鉴定3-CMC及其代谢产物的可能性是诊断该物质暴露的宝贵工具，无论是低剂量暴露还是数小时后的暴露，在临床和法医毒理学的各种应用中，如酒后驾车、药物辅助犯罪和中毒成瘾等方面都具有重要意义。DBS被证明是一种可靠的技术手段，可用于采集、储存和纯化用于检测3-CMC及其代谢产物的血液样本。
