利用四极杆-orbitrap LC-MS/MS 对斑马鱼、HLMs 和 S9 馏分中的依托咪酯和美托咪酯代谢物进行鉴定和定性，以用于药物控制。

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography B Pub Date : 2024-11-21 DOI:10.1016/j.jchromb.2024.124374

Shihao Zhong , Shiyang Qin , Yuanfeng Wang , Huan Li , Xiaoyi Wang , Tianruomei Chai , Jianghai Lu

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引用次数: 0

摘要

依托咪酯是一种常见的非巴比妥类麻醉剂，具有精神活性，而依托咪酯的结构修饰剂--安托咪酯也具有同样的精神活性，两者的滥用现象逐渐加剧。本研究首次利用液相色谱-高分辨质谱法（LC-HRMS），对依托咪酯和安托咪酯及其在受精后4天（4dpf）斑马鱼、受精后4个月（4mpf）斑马鱼、人类肝脏微粒体（HLMs）和人类肝脏S9馏分中的代谢谱进行了研究。结果发现了 14 种依托咪酯代谢物和 11 种美托咪酯代谢物，相关代谢途径包括单羟基化、二羟基化、脱氢、N-脱烷基化、O-脱烷基化、氧化、N-葡萄糖醛酸化、O-葡萄糖醛酸化和结合。依托咪酯酸（E6 和 M6）被认为是监测依托咪酯及其类似物滥用情况的常用生物标记物。两种特征代谢物（E4 和 M4）可分别用作监测依托咪酯或美托咪酯滥用情况的生物标记物。脱烷基化、羟基化和葡萄糖醛酸化是依托咪酯和甲哌咪酯的主要代谢途径。研究还首次比较了三种代谢模型的代谢特征差异。本研究的结果可为依托咪酯和美托咪酯滥用目标化合物的检测以及类似物质的代谢分析提供重要参考。

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Identification and characterization of etomidate and metomidate metabolites in zebrafish, HLMs and S9 fraction by quadrupole-orbitrap LC-MS/MS for drug control

Etomidate is a common non-barbiturate anesthetic with psychoactivity, and metomidate, a structural modifier of etomidate, also has the same psychoactive effect, and the abuse of both has gradually intensified. In this study, etomidate, metomidate and their metabolic profiles with 4 days postfertilization (4dpf) zebrafish, 4 months postfertilization (4mpf) zebrafish, human liver microsomes (HLMs) and human liver S9 fraction were investigated using Liquid chromatography with high resolution mass spectrometry (LC-HRMS) for the first time. 14 etomidate metabolites and 11 metomidate metabolites were found, and the related metabolic pathways included monohydroxylation, dihydroxylation, dehydrogenation, N-dealkylation, O-dealkylation, oxidation, N-glucuronidation, O-glucuronidation and combination. Etomidate acid (E6 and M6) was considered a common biomarker for monitoring the abuse of etomidate and its analogues. Two characteristic metabolites (E4 and M4) could be used as biomarkers to monitor etomidate or metomidate abuse, respectively. Dealkylation, hydroxylation and glucuronidation were the main metabolic pathways of etomidate and metomidate. The differences in metabolic profiles of the three metabolic models were also compared for the first time. The results of this study can provide important reference for the detection of target compounds against the abuse of etomidate and metomidate, and the metabolic analysis of similar substances.

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.