PMID- 38500459 OWN - NLM STAT- MEDLINE DCOM- 20240320 LR - 20240320 IS - 1004-5619 (Print) IS - 1004-5619 (Linking) VI - 40 IP - 1 DP - 2024 Feb 25 TI - Toxicokinetics of MDMA and Its Metabolite MDA in Rats. PG - 37-42 LID - 1004-5619(2024)01-0037-06 [pii] LID - 10.12116/j.issn.1004-5619.2022.320201 [doi] AB - 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), R(2)=0.974 6; T=7.397 3C(-0.694), R(2)=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. FAU - Yu, Wei-Guang AU - Yu WG AD - School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China. AD - Key Laboratory of the Ministry of Public Security for Toxicological Analysis of the Tribunal, Jinzhong 030600, Shanxi Province, China. FAU - He, Qiang AU - He Q AD - School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China. AD - Key Laboratory of the Ministry of Public Security for Toxicological Analysis of the Tribunal, Jinzhong 030600, Shanxi Province, China. FAU - Wang, Zheng-di AU - Wang ZD AD - School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China. AD - Key Laboratory of the Ministry of Public Security for Toxicological Analysis of the Tribunal, Jinzhong 030600, Shanxi Province, China. FAU - Tian, Cheng-Jun AU - Tian CJ AD - Yuxian Public Security Bureau of Yangquan City, Yangquan 045000, Shanxi Province, China. FAU - Wang, Jin-Kai AU - Wang JK AD - School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China. AD - Key Laboratory of the Ministry of Public Security for Toxicological Analysis of the Tribunal, Jinzhong 030600, Shanxi Province, China. FAU - Zheng, Qian AU - Zheng Q AD - School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China. AD - Key Laboratory of the Ministry of Public Security for Toxicological Analysis of the Tribunal, Jinzhong 030600, Shanxi Province, China. FAU - Ren, Fei AU - Ren F AD - Taiyuan Public Security Bureau, Taiyuan 030000, China. FAU - Zhang, Chao AU - Zhang C AD - School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China. AD - Key Laboratory of the Ministry of Public Security for Toxicological Analysis of the Tribunal, Jinzhong 030600, Shanxi Province, China. FAU - Wang, You-Mei AU - Wang YM AD - National Drug Laboratory, Centre for Counter-Narcotics Information Technology, Ministry of Public Security, Beijing 100193, China. FAU - Xu, Peng AU - Xu P AD - National Drug Laboratory, Centre for Counter-Narcotics Information Technology, Ministry of Public Security, Beijing 100193, China. FAU - Wei, Zhi-Wen AU - Wei ZW AD - School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China. AD - Key Laboratory of the Ministry of Public Security for Toxicological Analysis of the Tribunal, Jinzhong 030600, Shanxi Province, China. FAU - Yun, Ke-Ming AU - Yun KM AD - School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China. AD - Key Laboratory of the Ministry of Public Security for Toxicological Analysis of the Tribunal, Jinzhong 030600, Shanxi Province, China. LA - eng LA - chi PT - Journal Article PL - China TA - Fa Yi Xue Za Zhi JT - Fa yi xue za zhi JID - 9426151 RN - CK833KGX7E (Amphetamine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - 4764-17-4 (3,4-Methylenedioxyamphetamine) RN - 0 (Saline Solution) RN - 9E273KL7HS (1-(4-methylphenyl)propane-2-amine) RN - 0 (Amphetamines) SB - IM MH - Rats MH - Animals MH - Amphetamine MH - *N-Methyl-3,4-methylenedioxyamphetamine/toxicity MH - *3,4-Methylenedioxyamphetamine/analysis MH - Toxicokinetics MH - Saline Solution MH - *Amphetamines OTO - NOTNLM OT - 3,4-methylenedioxy- N-methylamphetamine OT - 4,5-methylene dioxy amphetamine OT - forensic medicine OT - model OT - rats OT - toxicokinetics OT - toxicology EDAT- 2024/03/19 06:44 MHDA- 2024/03/20 06:45 CRDT- 2024/03/19 03:33 PHST- 2024/03/20 06:45 [medline] PHST- 2024/03/19 06:44 [pubmed] PHST- 2024/03/19 03:33 [entrez] AID - 1004-5619(2024)01-0037-06 [pii] AID - 10.12116/j.issn.1004-5619.2022.320201 [doi] PST - ppublish SO - Fa Yi Xue Za Zhi. 2024 Feb 25;40(1):37-42. doi: 10.12116/j.issn.1004-5619.2022.320201.