利用液相色谱-串联质谱法对死后尿液中的 7- 和 8- 羟基唑吡坦进行定性分析,并发现新型唑吡坦代谢物。

IF 2.8 4区 医学 Q2 TOXICOLOGY
Forensic Toxicology Pub Date : 2022-07-01 Epub Date: 2022-01-04 DOI:10.1007/s11419-021-00611-9
Koji Yamaguchi, Hajime Miyaguchi, Youkichi Ohno, Yoshimasa Kanawaku
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引用次数: 0

摘要

目的:唑吡坦(ZOL)是一种催眠药,有时被用于毒品犯罪。了解 ZOL 的代谢对证明 ZOL 摄入量非常重要。在本研究中,我们合成了吡啶环上带有羟基的羟基唑吡旦标准品,并对其进行了分析,以证明它们存在于尸体尿液中。我们还使用液相色谱-三重四极杆质谱法(LC-QqQMS)和液相色谱-四极杆飞行时间质谱法(LC-QqTOFMS)在尿样中寻找新型 ZOL 代谢物。比较了合成标准品和尸体尿液提取物的保留时间。为了寻找新的 ZOL 代谢物,首先,采用数据采集法分析尿液提取物,选出显示 ZOL 特征碎片模式的峰值。其次,采集这些峰在不同碰撞能量下的产物离子谱,并选择可用于多反应监测(MRM)的碎片。最后,利用尿液提取物对 MRM 参数进行了优化。还利用 LC-QqTOFMS 对这些峰进行了分析:结果:证实尿液中含有 7OHZ 和 8OHZ。羟唑吡啶中的最高峰为 7OHZ。发现的新型代谢物包括唑吡旦二氢二醇及其葡萄糖醛酸苷、ZOL 和二羟基唑吡旦的半胱氨酸加合物以及羟基唑吡旦的葡萄糖醛酸苷:结论:新型代谢物的出现揭示了新的代谢途径,其中包括在吡啶环上形成环氧化物作为中间体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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.

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.

Purpose: 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).

Methods: 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.

Results: 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.

Conclusions: The presence of novel metabolites revealed new metabolic pathways, which involve formation of an epoxide on the pyridine ring as an intermediate.

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来源期刊
Forensic Toxicology
Forensic Toxicology TOXICOLOGY-
CiteScore
5.80
自引率
9.10%
发文量
40
审稿时长
3 months
期刊介绍: The journal Forensic Toxicology provides an international forum for publication of studies on toxic substances, drugs of abuse, doping agents, chemical warfare agents, and their metabolisms and analyses, which are related to laws and ethics. It includes original articles, reviews, mini-reviews, short communications, and case reports. Although a major focus of the journal is on the development or improvement of analytical methods for the above-mentioned chemicals in human matrices, appropriate studies with animal experiments are also published. Forensic Toxicology is the official publication of the Japanese Association of Forensic Toxicology (JAFT) and is the continuation of the Japanese Journal of Forensic Toxicology (ISSN 0915-9606).
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