【摘要】 苏沃雷生、达利雷生和莱伯雷生作为新型催眠药物，近年来在药物辅助犯罪案件如迷奸与投毒中频见报道。然而，目前尚未见可同时高灵敏和高选择性检测人血液中上述3种药物的方法报道。本研究建立了一种基于超高效液相色谱-串联质谱（UPLC-MS/MS）技术，可同时定性及定量检测人血液中苏沃雷生、达利雷生和莱伯雷生的分析方法。优化了血液样本前处理流程，采用UPLC进行分离，并在电喷雾正离子及多反应监测模式下进行质谱检测。结果表明，3种目标物色谱峰形良好且分离效果佳，方法精密度及样品处理后的稳定性均符合相关要求。本方法灵敏度高，对苏沃雷生、莱伯雷生和达利雷生的检出限分别为0.05、0.06和0.07 ng/mL，定量限分别为0.17、0.21和0.24 ng/mL;3种药物的基质效应、回收率及准确度均满足生物样品分析要求；在0.25～100 ng/mL的浓度范围内，3种药物均呈现良好的线性关系，相关系数均大于0.998。本方法简便、快速、灵敏且稳定，适合日常法医毒物学检验鉴定工作，在相关药物的代谢动力学研究方面具有潜在的应用价值。更多还原

【Abstract】 uvorexant, daridorexant, and lemborexant, as a class of novel hypnotic agents, have been increasingly reported in cases of drug-facilitated crimes(DFCs), such as sexual assault and poisoning. However, highly selective and sensitive methods for simultaneous detection of these drugs in human blood remain scarce. This study aimed to develop and validate a method based on ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) for simultaneous qualitative and quantitative analysis of these drugs in blood. The sample preparation procedure was systematically investigated and optimized. Chromatographic separation was achieved using UPLC, and MS detection was performed under positive electrospray ionization(ESI~+) in multiple reaction monitoring(MRM) mode. The results demonstrated excellent chromatographic performance, with well-resolved peaks and satisfactory separation for all three target analytes. The method exhibited acceptable precision and postpreparative stability. It proved to be highly sensitive, with limits of detection(LOD) of 0.05, 0.06 and 0.07 ng/mL,and limits of quantification(LOQ) of 0.17, 0.21 and 0.24 ng/mL, for suvorexant, lemborexant, and daridorexant,respectively. The matrix effect, recovery, and accuracy for all analytes met the predefined criteria for bioanalytical method validation. Excellent linearity was observed for the three drugs over a concentration range of 0.25 to100 ng/mL, with correlation coefficients(r~2) greater than 0.998. In conclusion, the developed UPLC-MS/MS method was simple, rapid, sensitive, and reliable, and suitable for routine application in forensic toxicological analysis, showing potential in pharmacokinetic studies of these drugs.更多还原