法医学杂志

法医学杂志 ›› 2021, Vol. 37 ›› Issue (4): 493-499.DOI: 10.12116/j.issn.1004-5619.2021.310401

所属专题： 新精神活性物质

• 专题 • 上一篇    下一篇

新精神活性物质4F-MDMB-BUTINACA在斑马鱼体内的代谢

岳琳娜1，2， 向平1， 宋粉云2， 沈保华1， 严慧1   

  1. 1. 司法鉴定科学研究院 上海市法医学重点实验室 司法部司法鉴定重点实验室 上海市司法鉴定专业技术服务平台，上海 200063； 2. 广东药科大学药学院，广东 广州 510006
  • 发布日期:2021-08-25 出版日期:2021-08-28
  • 通讯作者: 沈保华，男，硕士，主任法医师，主要从事法医毒物分析；E-mail：shenbh@ssfjd.cn 严慧，女，博士，副研究员，主要从事法医毒物学研究；E-mail：yanh501@163.com
  • 作者简介:岳琳娜（1995—），女，硕士研究生，主要从事现代分析方法在中药质量控制中的应用研究；E-mail：yuelinna95@163.com
  • 基金资助:
    上海市自然科学基金资助项目（19ZR1458800）；司法部司法鉴定重点实验室资助项目；上海市法医学重点实验室资助项目（21DZ2270800）；上海市司法鉴定专业技术服务平台资助项目（19DZ2292700）

Metabolism of New Psychoactive Substances 4F-MDMB-BUTINACA in Zebrafish

YUE Lin-na1,2, XIANG Ping1, SONG Fen-yun2, SHEN Bao-hua1, YAN Hui1   

  1. 1. Shanghai Key Laboratory of Forensic Medicine, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai Forensic Service Platform, Academy of Forensic Science, Shanghai 200063, China; 2. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
  • Online:2021-08-25 Published:2021-08-28

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摘要： 目的 通过建立斑马鱼模型研究合成大麻素2-[1-（4-氟丁基）-1H-吲唑-3-甲酰氨基]-3，3-二甲基丁酸甲酯（4F-MDMB-BUTINACA）的体内代谢转化途径。 方法 将6条成年斑马鱼随机分为空白对照组和实验组，每组3条。实验组斑马鱼在4F-MDMB-BUTINACA（1 μg/mL）药液中暴露染毒24 h后转移到清水中清洗3次，进行样品前处理，待仪器分析。空白对照组斑马鱼不暴露于4F-MDMB-BUTINACA。采用液相色谱-高分辨质谱技术结合Mass Frontier软件对4F-MDMB-BUTINACA及其代谢产物进行质谱解析和结构分析。 结果 斑马鱼体内共检测到4F-MDMB-BUTINACA的26个代谢产物，包括18个Ⅰ相代谢产物以及8个Ⅱ相代谢产物。4F-MDMB-BUTINACA在斑马鱼体内的Ⅰ相代谢途径主要包括酯水解、脱烷基化、氧化脱氟和羟基化，葡萄糖醛酸结合反应是主要的Ⅱ相代谢转化途径。 结论 酯水解代谢产物Md24和酯水解脱氢代谢产物Md25被推荐为4F-MDMB-BUTINACA滥用的良好生物标志物。

关键词: 法医学；毒物分析；合成大麻素类；代谢途径；液相色谱法；高分辨质谱；2-[1-（4-氟丁基）-1H-吲唑-3-甲酰氨基]-3, 3-二甲基丁酸甲酯；斑马鱼

Abstract: Objective To study the metabolic transformation pathways of 4F-MDMB-BUTINACA in vivo by establishing zebrafish models. Methods Six adult zebrafish were randomly divided into blank control group and experimental group, with three fish in each group. After the zebrafish in the experimental group were exposed to 1 μg/mL 4F-MDMB-BUTINACA for 24 h, they were transferred to clean water and cleaned three times, then pretreated for instrumental analysis. The zebrafish in blank control group were not exposed to 4F-MDMB-BUTINACA. Mass spectrometry and structural analysis of 4F-MDMB-BUTINACA and its metabolites were conducted by liquid chromatography-high resolution mass spectrometry and Mass Frontier software. Results A total of twenty-six metabolites of 4F-MDMB-BUTINACA were identified in zebrafish, including eighteen phase Ⅰ metabolites and eight phase Ⅱ metabolites. The main metabolic pathways of phase Ⅰ metabolites of 4F-MDMB-BUTINACA in zebrafish were ester hydrolysis, N-dealkylation, oxidative defluorination and hydroxylation, while the main metabolic pathway of phase Ⅱ metabolites was glucuronidation. Conclusion Metabolite Md24 （ester hydrolysis） and Md25 （ester hydrolysis combined with dehydrogenation） would be recommended to be potentially good biomarkers for abuse of 4F-MDMB-BUTINACA.

Key words: forensic medicine, toxicological analysis, synthetic cannabinoids, metabolic pathway, liquid chromatography （LC）, high resolution mass spectrometry （HRMS）, 4F-MDMB-BUTINACA, zebrafish

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