Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography-tandem mass spectrometry.
Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography-tandem mass spectrometry.
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采用液相色谱-串联质谱法定性分析7-和8-羟基唑吡坦并发现死后尿液中的新型唑吡坦代谢物。
DOI：
10.1007/s11419-021-00611-9
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发表时间：
2022-07
影响因子：
2.2
通讯作者：
Kanawaku, Yoshimasa
中科院分区：
文献类型：
--
作者：
Yamaguchi, Koji;Miyaguchi, Hajime;Ohno, Youkichi;Kanawaku, Yoshimasa
唑吡坦(ZOL)是一种催眠药，有时用于毒品犯罪。了解ZOL的代谢对于证明ZOL的摄入量很重要。在这项研究中，我们合成了吡啶环上带有羟基的羟基唑吡啶标准品，并对它们进行了分析，以证明它们在死后尿液中的存在。同时，我们还利用液相色谱-三重四极杆质谱仪(LC-QqQMS)和LC-四极杆飞行时间质谱仪(LC-QqTOFMS)在尿样中寻找新的ZOL代谢物。合成了7-和8-羟基唑烷(分别为70HZ和80HZ)，并用LC-QQMS对其进行了分析。比较合成标准品和死后尿液提取物的保留时间。为了寻找新的ZOL代谢物，首先，用数据依赖采集法对尿液提取物进行分析，并选择显示ZOL特征碎片模式的峰。其次，获得了这些峰在不同碰撞能下的产物离子光谱，并选择了可用于多反应监测(MRM)的碎片。最后利用尿液提取液对磁共振波谱参数进行了优化。用LC-QqTOFMS对这些峰进行了分析。证实尿液中存在70HZ和80HZ。羟基唑吡啶中最高的峰位于7OHZ。新发现的代谢物为唑吡坦二氢二醇及其葡萄糖醛酸苷、ZOL与二氢(羟基)唑吡坦的半胱氨酸加合物和羟基唑吡啶的葡醛酸衍生物。新代谢物的出现揭示了新的代谢途径，其中包括作为中间体在吡啶环上形成环氧化物。网上版载有补充材料，可在10.1007/s11419021-00611-9查阅。
Zolpidem (ZOL) is a hypnotic sometimes used in drug-facilitated crimes. Understanding ZOL metabolism is important for proving ZOL intake. In this study, we synthesized standards of hydroxyzolpidems with a hydroxy group attached to the pyridine ring and analyzed them to prove their presence in postmortem urine. We also searched for novel ZOL metabolites in the urine sample using liquid chromatography–triple quadrupole mass spectrometry (LC-QqQMS) and liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QqTOFMS). 7- and 8-Hydroxyzolpidem (7OHZ and 8OHZ, respectively) were synthesized and analyzed using LC-QqQMS. Retention times were compared between the synthetic standards and extracts of postmortem urine. To search for novel ZOL metabolites, first, the urine extract was analyzed with data-dependent acquisition, and the peaks showing the characteristic fragmentation pattern of ZOL were selected. Second, product ion spectra of these peaks at various collision energies were acquired and fragments that could be used for multiple reaction monitoring (MRM) were chosen. Finally, MRM parameters were optimized using the urine extract. These peaks were also analyzed using LC-QqTOFMS. The presence of 7OHZ and 8OHZ in urine was confirmed. The highest peak among hydroxyzolpidems was assigned to 7OHZ. The novel metabolites found were zolpidem dihydrodiol and its glucuronides, cysteine adducts of ZOL and dihydro(hydroxy)zolpidem, and glucuronides of hydroxyzolpidems. The presence of novel metabolites revealed new metabolic pathways, which involve formation of an epoxide on the pyridine ring as an intermediate. The online version contains supplementary material available at 10.1007/s11419-021-00611-9.
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影响因子：
2.5
作者：
Tsujikawa, K;Kuwayama, K;Kishi, T
通讯作者：
Kishi, T
DOI：
10.1016/0378-4347(92)80277-w
发表时间：
1992-10-23
期刊：
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS
影响因子：
--
作者：
ASCALONE, V;FLAMINIO, L;MORSELLI, PL
通讯作者：
MORSELLI, PL
影响因子：
2.9
作者：
Feng, Xueyi;Chen, Hang;Shen, Min
通讯作者：
Shen, Min
影响因子：
2.5
作者：
Schwope, David M.;DePriest, Anne;Heltsley, Rebecca
通讯作者：
Heltsley, Rebecca
影响因子：
2.2
作者：
Yamaguchi, Koji;Goda, Takahiro;Ohno, Youkichi
通讯作者：
Ohno, Youkichi