Abstract：
Zolpidem, N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide, is a hypnotic agent widely used in clinical practice but is detected in many clinical cases of fatal intoxication and suicide. In forensic toxicology, the precise determination of zolpidem concentration in blood is a must to provide concrete evidence of death by zolpidem poisoning. However, the concentrations of zolpidem in blood at autopsy often differ from those at the estimated time of death. In the present study, we found that zolpidem was degraded by hemoglobin (Hb) via the Fenton reaction at various temperatures. The mechanism underlying zolpidem degradation involved the oxidation of its linker moiety. The MS and MS/MS spectra obtained by liquid chromatography quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap-MS) showed the formation of 2-hydroxy-N,N-dimethyl-2-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)acetamide (2-OH ZOL) in Hb/H2O2 solution incubated with zolpidem and in the blood of several individuals who died from ingestion of zolpidem. These results suggest that 2-OH ZOL is the post-mortem product of zolpidem degradation by Hb via the Fenton reaction.
摘要：
唑吡坦,N,N-二甲基-2-[6-甲基-2-(4-甲基苯基)咪唑并[1,2-a]吡啶-3-基]乙酰胺，是一种在临床实践中广泛使用的催眠药，但在许多致命中毒和自杀的临床病例中被检测到。在法医毒理学中，精确测定唑吡坦在血液中的浓度是提供唑吡坦中毒死亡的具体证据的必要条件。然而,尸检时血液中唑吡坦的浓度通常与估计死亡时间的浓度不同。在本研究中,我们发现唑吡坦在不同温度下通过Fenton反应被血红蛋白（Hb）降解。唑吡坦降解的潜在机制涉及其接头部分的氧化。通过液相色谱四极杆-Orbitrap质谱（LC-Q-Orbitrap-MS）获得的MS和MS/MS光谱显示形成2-羟基-N，与唑吡坦一起孵育的Hb/H2O2溶液中的N-二甲基-2-（6-甲基-2-（对甲苯基）咪唑并[1,2-a]吡啶-3-基）乙酰胺（2-OHZOL）和因摄入唑吡坦而死亡的几个人的血液中。这些结果表明，2-OHZOL是唑吡坦通过Fenton反应被Hb降解的事后产物。
