School of Investigation, People's Public Security University of China, Beijing 100038, China.
Forensic Science Service of Beijing Public Security Bureau, Key Laboratory of Forensic Toxicology, Ministry of Public Security, Beijing 100192, China.
J Pharm Biomed Anal. 2024 Mar 15;240:115936. doi: 10.1016/j.jpba.2023.115936. Epub 2023 Dec 23.
As one of the most widely abused designer benzodiazepines in the world, etizolam has been found in many cases in many countries. In this study, UPLC-Q-Exactive-MS was used for the first time to establish a dynamic change model of etizolam and its metabolites in rats. Compared with previous studies, the detection sensitivity and reproducibility of the instrument were higher. In the experiment, we optimized the traditional pharmacokinetic model based on Gauss function. According to the significant difference of etizolam in the plasma elimination phase of rats, a new pharmacokinetic model based on Lorentz function was established to describe the dynamic changes of etizolam more rigorously, which made the error effects lower and the accuracy of the pharmacokinetic parameters was improved. At the same time, the pharmacokinetic parameters of etizolam were compared with four other designer benzodiazepines reported in previous studies in rats, and we found the direct reason for the popularity of etizolam in the NPS market and explored the future development of etizolam for the first time. In addition, 21 metabolites were found through rat experiments to effectively detect etizolam abuse for a long time, of which 4 metabolites had the longest detection window and could be used as long-acting metabolites for experiments, which greatly prolongs the detection window and extends the time range in which etizolam was detected in real cases. This study is the first to conduct a systematic and comprehensive study on the metabolism and pharmacokinetics of etizolam and find out the direct reason for the prevalence of etizolam abuse, and we also discuss the development trend of etizolam in the future market of new psychoactive substances, which is beneficial for forensic experts to assess the trend of drug abuse and can provide reference for relevant drug control and drug treatment.
作为世界上滥用最多的苯二氮䓬类药物之一，艾司唑仑已在许多国家的许多案例中被发现。在本研究中，首次使用 UPLC-Q-Exactive-MS 建立了艾司唑仑及其代谢物在大鼠体内的动态变化模型。与以前的研究相比，该仪器具有更高的检测灵敏度和重现性。在实验中，我们优化了基于高斯函数的传统药代动力学模型。根据大鼠血浆中艾司唑仑消除相的显著差异，建立了基于洛伦兹函数的新药代动力学模型，以更严格地描述艾司唑仑的动态变化，从而降低误差效应，提高药代动力学参数的准确性。同时，将艾司唑仑的药代动力学参数与之前研究中报道的其他四种苯二氮䓬类药物进行了比较，我们发现了艾司唑仑在 NPS 市场上流行的直接原因，并首次探索了艾司唑仑的未来发展。此外，通过大鼠实验发现了 21 种代谢物，可有效检测艾司唑仑的长期滥用，其中 4 种代谢物的检测窗口最长，可作为实验的长效代谢物，极大地延长了检测窗口，延长了艾司唑仑在实际案例中的检测时间范围。本研究首次对艾司唑仑的代谢和药代动力学进行了系统全面的研究，找出了艾司唑仑滥用流行的直接原因，同时还探讨了艾司唑仑在未来新型精神活性物质市场中的发展趋势，这有利于法医专家评估药物滥用的趋势，并为相关药物管制和药物治疗提供参考。
