法医学杂志

法医学杂志 ›› 2024, Vol. 40 ›› Issue (1): 37-42.DOI: 10.12116/j.issn.1004-5619.2022.320201

• 论著 • 上一篇    下一篇

MDMA及其代谢物MDA在大鼠体内的毒物代谢动力学

于维光1,2(), 贺强1,2, 王铮迪1,2, 田成俊3, 王锦凯1,2, 郑茜1,2, 任飞4, 张潮1,2, 王优美5, 徐鹏5, 尉志文1,2(), 贠克明1,2()   

  1. 1.山西医科大学法医学院，山西 晋中 030600
    2.法庭毒物分析公安部重点实验室，山西 晋中 030600
    3.阳泉市盂县公安局，山西 阳泉 045000
    4.太原市公安局，山西 太原 030000
    5.公安部禁毒情报技术中心国家毒品实验室，北京 100193
  • 收稿日期:2022-02-14 发布日期:2024-03-19 出版日期:2024-02-25
  • 通讯作者: 尉志文,贠克明
  • 作者简介:于维光（1995—），男，硕士研究生，主要从事法医毒理学和法医毒物分析研究；E-mail：yuweiguang1995@163.com
  • 基金资助:
    国家重点研发计划资助项目(2018YFC0807403);国家自然科学基金重点资助项目(82130056);山西省高等学校科技创新资助项目(2019L0413)

Toxicokinetics of MDMA and Its Metabolite MDA in Rats

Wei-guang YU1,2(), Qiang HE1,2, Zheng-di WANG1,2, Cheng-jun TIAN3, Jin-kai WANG1,2, Qian ZHENG1,2, Fei REN4, Chao ZHANG1,2, You-mei WANG5, Peng XU5, Zhi-wen WEI1,2(), Ke-ming YUN1,2()   

  1. 1.School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China
    2.Key Laboratory of the Ministry of Public Security for Toxicological Analysis of the Tribunal, Jinzhong 030600, Shanxi Province, China
    3.Yuxian Public Security Bureau of Yangquan City, Yangquan 045000, Shanxi Province, China
    4.Taiyuan Public Security Bureau, Taiyuan 030000, China
    5.National Drug Laboratory, Centre for Counter-Narcotics Information Technology, Ministry of Public Security, Beijing 100193, China
  • Received:2022-02-14 Online:2024-03-19 Published:2024-02-25
  • Contact: Zhi-wen WEI, Ke-ming YUN

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摘要：

目的 探究单次和连续给药3，4-亚甲基二氧基甲基苯丙胺（3，4-methylenedioxy-N-methylamphetamine，MDMA）后，MDMA及其代谢物4，5-亚甲基二氧基苯丙胺（4，5-methylene dioxy amphetamine，MDA）在大鼠体内的毒物代谢动力学差异，为MDMA的法医学鉴定提供数据依据。 方法 单次给药组取24只大鼠随机分为5、10、20 mg/kg实验组和对照组，每组6只，实验组腹腔注射给药MDMA，对照组经腹腔注射给药与实验组同等体积的生理盐水。给药后5 min、30 min、1 h、1.5 h、2 h、4 h、6 h、8 h、10 h、12 h通过内眦动脉取血0.5 mL。连续给药组取24只大鼠随机分为实验组（18只）和对照组（6只）。实验组连续腹腔注射递增给药MDMA 7 d，每日给药剂量分别为5、7、9、11、13、15、17 mg/kg，对照组经腹腔注射给药与实验组同等体积的生理盐水。第8天将实验组大鼠随机分为5、10、20 mg/kg剂量组，每组6只，腹腔注射给药MDMA，对照组经腹腔注射与实验组同等体积的生理盐水。给药后5 min、30 min、1 h、1.5 h、2 h、4 h、6 h、8 h、10 h、12 h通过内眦动脉取血0.5 mL。使用液相色谱-三重四极杆串联质谱检测MDMA和MDA含量，运用统计学软件进行数据分析。 结果 单次给药组血浆中MDMA在给药后5 min达到峰浓度，MDA在给药后1 h达到峰浓度，MDMA和MDA的最长检出时限为12 h。连续给药组第8天MDMA在给药后30 min达到峰浓度，MDA在给药后1.5 h达到峰浓度，MDMA和MDA的最长检出时限为10 h。单次给药组和连续给药组检出时限内MDMA和MDA质量浓度比与给药时间的非线性拟合方程分别为T=10.362C-1.183，R2=0.974 6；T=7.397 3C-0.694，R2=0.961 5（T为给药时间，C为MDMA和MDA在血浆中的质量浓度比）。 结论 本研究得到的MDMA及其代谢物MDA在单次和连续给药大鼠体内毒物代谢动力学数据（达峰浓度、达峰时间、检测时限和质量浓度比与给药时间的关系）为相关法医学鉴定提供了理论基础和数据依据。

关键词: 法医学, 毒物化学, 毒物代谢动力学, 3, 4-亚甲基二氧基甲基苯丙胺, 4, 5-亚甲基二氧基苯丙胺, 模型, 大鼠

Abstract:

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine （MDMA） and its metabolite 4,5-methylene dioxy amphetamine （MDA） in rats after single and continuous administration of MDMA, providing reference data for the forensic identification of MDMA. Methods A total of 24 rats in the single administration group were randomly divided into 5, 10 and 20 mg/kg experimental groups and the control group, with 6 rats in each group. The experimental group was given intraperitoneal injection of MDMA, and the control group was given intraperitoneal injection of the same volume of normal saline as the experimental group. The amount of 0.5 mL blood was collected from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. In the continuous administration group, 24 rats were randomly divided into the experimental group （18 rats） and the control group （6 rats）. The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5, 7, 9, 11, 13, 15, 17 mg/kg per day, respectively, while the control group was given the same volume of normal saline as the experimental group by intraperitoneal injection. On the eighth day, the experimental rats were randomly divided into 5, 10 and 20 mg/kg dose groups, with 6 rats in each group. MDMA was injected intraperitoneally, and the control group was injected intraperitoneally with the same volume of normal saline as the experimental group. On the eighth day, 0.5 mL of blood was taken from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels, and statistical software was employed for data analysis. Results In the single-administration group, peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration, respectively, with the largest detection time limit of 12 h. In the continuous administration group, peak concentrations were reached at 30 min and 1.5 h after administration, respectively, with the largest detection time limit of 10 h. Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows: T=10.362C-1.183, R2=0.974 6; T=7.397 3C-0.694, R2=0.961 5 （T: injection time; C: concentration ratio of MDMA to MDA in plasma）. Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats, obtained through single and continuous administration, including peak concentration, peak time, detection time limit, and the relationship between concentration ratio and administration time, provide a theoretical and data foundation for relevant forensic identification.

Key words: forensic medicine, toxicology, toxicokinetics, 3,4-methylenedioxy-N-methylamphetamine, 4,5-methylene dioxy amphetamine, model, rats

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