摘要
目的研究甲卡西酮及其代谢物卡西酮、麻黄碱和伪麻黄碱的毒物代谢动力学特征。方法大鼠分别以甲卡西酮17.25mg/kg和34.5mg/kg经腹腔注射给药,给药后不同时间点经内眦静脉采血,血液中甲卡西酮及其代谢物卡西酮、麻黄碱和伪麻黄碱用HPLC-MS/MS定性、定量检测,DAS3.2.8药代动力学软件拟合动力学方程并计算毒物代谢动力学参数。结果甲卡西酮原体在大鼠血液中的代谢动力学过程符合一级吸收二室开放模型,达峰时间在给予剂量间无明显差异,剂量可以明显导致消除半衰期的延长。低剂量组代谢动力学方程为C=10515.971×e^(-0.024t)-10515.919×e^(-0.144t),高剂量组代谢动力学方程为C=12410.093×e^(-0.015t)-12409.465×e^(-0.169t)。甲卡西酮和卡西酮的检出时限为24h,麻黄碱和伪麻黄碱的检出时限均为2h。甲卡西酮和卡西酮在血液中的浓度比随注射时间的变化不受药物在体内的吸收过程影响,呈指数关系。结论本研究建立的甲卡西酮毒物代谢动力学方程和参数,代谢物的检出时限及与吸毒时间的变化规律可以为甲卡西酮吸毒鉴定的合理取样,原型和代谢物的检出,浓度关系推断吸毒时间以及法医学鉴定提供理论和实验依据。
Objective To investigate the toxicokinetic profiles of methcathinone and its metabolites cathinone, ephedrine and pseudoephedrine in rats. Methods The rats were administered methcathinone with 17.25 mg/kg and 34.5 mg/kg respectively by intraperitoneally. Blood samples were collected via the medial canthus vein at different time points after administration. Methcathinone and its metabolites, cathinone, ephedrine and pseudoephedrine, were analyzed by HPLC-MS/MS. The data were fitted by DAS3.2.8 software. Results The mean blood concentration-time profile of methcathinone was in accordance with the first-order absorption two compartment open model. There was no significant difference in the peak time between doses. The dose could significantly prolong the elimination half-life. The kinetic equation of methcathinone in low dose group was C=10515.971× e^(-0.024 t)-10515.919×e^(-0.144 t), and that in high dose group was C=12410.093×e^(-0.015 t)-12409.465×e^(-0.169 t). The detection time limit of methcathinone and cathinone was 24 hours, and that of ephedrine and pseudoephedrine was 2 hours. The concentration ratio of methcathinone to cathinone in blood was not affected by the absorption process of the drug in vivo and showed an exponential relationship with the injection time. Conclusion In this study, the toxicokinetics equation and parameters of methcathinone, the detection time limit of metabolites and the change rule of drug use time were established. It would provide theoretical and experimental basis for the rational sampling of methcathinone abuse and the forensic identification. Meanwhile, it would infer the use time from the concentration relationship of methcathinone and cathinone.
作者
尉志文
陈佳晖
张潮
禹明筠
杨秀秀
王学志
孟宇珍
杨睿
王优美
徐鹏
贠克明
Wei Zhiwen;Chen Jiahui;Zhang Chao;Yu Mingyun;Yang Xiuxiu;WangXuezhi;Meng Yuzhen;Yang Rui;Wang Youmei;Xu Peng;Yun Keming(Shanxi Medical University,Jinzhong City,Shanxi Province,030600;Key Laboratory of Toxicology Analysis,Ministry of Public Security,Jinzhong City,Shanxi Province,030600;National Drug Laboratory,Anti-Drug Intelligence Technology Center,Ministry of Public Security,Beijing,100193;Anti Drug Information Technology Center of the Ministry of Public Security,Beijing,100193)
出处
《中国法医学杂志》
CSCD
2021年第4期369-372,378,共5页
Chinese Journal of Forensic Medicine
基金
国家重点研发计划项目资助(2018YFC0807403,2017YFC0803504)。
