Objectives: 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.
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。.
Keywords: 3,4-methylenedioxy- N-methylamphetamine; 4,5-methylene dioxy amphetamine; forensic medicine; model; rats; toxicokinetics; toxicology.