新型合成大麻素MDMB-4en-PINACA、ADB-BUTINACA在大鼠体内代谢研究  

Probing into MDMB-4en-PINACA and ADB-BUTINACA (Novel Synthetic Cannabinoids) about Their Metabolism in Rats

作　　者：蔡玉刚 吴永富 周钶 龙兵[2] 陆银 周达江[3] 代勇[2] 王燕军[4] CAI Yugang;WU Yongfu;ZHOU Ke;LONG Bing;LU Yin;ZHOU Dajiang;DAI Yong;WANG Yanjun(Institute of Forensic Science of Luzhou Public Security Bureau,Luzhou 646000,Sichuan,China;Sichuan Police College,Luzhou 646000,Sichuan,China;Institute of Forensic Science of Chengdu Public Security Bureau,Chengdu 610017,China;Criminal Investigation Division,Sichuan Provincial Public Security Department,Chengdu 610015,China)

机构地区：[1]泸州市公安局刑事科学技术研究所,四川泸州646000 [2]四川警察学院,四川泸州646000 [3]成都市公安局刑事科学技术研究所,成都610017 [4]四川省公安厅刑侦局,成都610015

出　　处：《刑事技术》2023年第4期394-404,共11页Forensic Science and Technology

基　　金：四川省省级大学生创新创业训练项目(S202112212073);四川省公安厅2021年度厅级科研项目(2021YYCX02);四川省科技厅重大科研项目(2020YFS0349)。

摘　　要：通过动物实验探索MDMB-4en-PINACA和ADB-BUTINACA两种合成大麻素在大鼠体内的代谢方式,确定主要代谢物和代谢标记物。利用高效液相色谱–四极杆飞行时间质谱(HPLC-QTOF)筛查给药后MDMB-4en-PINACA和ADB-BUTINACA在大鼠血液和肝组织中可能存在的代谢物;12只SD大鼠随机分为两组,禁食12 h,按1.0 mg/kg腹腔注射给药,第一组为MDMB-4en-PINACA实验组,第二组为ADB-BUTINACA实验组,在给药后5、15、30、60、120 min分别处死取血液和肝组织,经处理后检测分析。结果表明:合成大麻素MDMB-4en-PINACA进入大鼠体内后,经双键氧化羧基化、酯水解、4-脱戊烯基化、羟基化代谢成相应的代谢物;ADB-BUTINACA进入大鼠体内后,经水解、4-脱烷基化、4-丁基羟基化、羟基化代谢成相应的代谢物。根据检测大鼠血液和肝组织中成分的响应强度,MDMB-4en-PINACA代谢物主要有4-戊烯基氧化羟基化代谢物(编号M6),4-戊烯基氧化羧基化代谢物(编号M7),丁酸甲酯水解代谢物(编号M2)和进一步羟基化代谢物(编号M3、M4、M5),n-脱烷烯基化代谢物(编号M1),确定MDMB-4en-PINACA代谢标记物为M1和M2。ADB-BUTINACA的代谢物主要有4-脱丁基化代谢物(编号A1)和甲酰胺基水解代谢物(编号A2),4-丁基羧基化代谢物(编号A3),4-丁基羟基化代谢物(编号A4),确定ADB-BUTINACA代谢标记物为A1和A2。Synthetic cannabinoids are of hallucinogenic effect equivalent to or even stronger than that of cannabis,being listed under the fi rst batch of new psychoactive substances controlled in China.There are many kinds of synthetic cannabinoids,among which MDMB-4en-PINACA and ADB-BUTINACA are recently the two ones of most active alkyl formyl indazole in the market.Such two synthetic cannabinoids have presumably not been reported about their metabolic researches in China.Thus,both the MDMB-4en-PINACA and ADB-BUTINACA were here probed into their metabolites from the blood and liver of rats.With 12 SD rats randomly divided into two equal groups:one for MDMB-4en-PINACA and the other for ADB-BUTINACA,each rat was fasted for 12 h and then intraperitoneally administered once by weight as per 1.0 mg/kg along with the two groups leaving one rat taken as the control that was not injected of drug yet executed just before administration.The remaining fi ve rats in each group administered of drug were respectively killed at 5,15,30,60 and 120 min after drug injection,having their blood and liver tissues received and successively analyzed into high performance liquid chromatography quadrupole time of flight mass spectrometry(HPLC-QTOF).The results showed that the experimental rats had MDMB-4en-PINACA metabolized into corresponding metabolites through double bond oxidative carboxylation,ester hydrolysis,4-depentenylation and hydroxylation,with ADB-BUTINACA being metabolized through hydrolysis,4-dealkylation,4-butyl hydroxylation and hydroxylation.According to the response intensity of components in blood and liver tissue of rat,MDMB-4en-PINACA mainly converted into its metabolites from pentenyl oxidative hydroxylation(No.M6),pentenyl oxidative carboxylation(No.M7),methyl butyrate hydrolysis(No.M2)and further hydroxylation(No.M3/M4/M5)and dealkylation(No.M1),demonstrating its metabolic markers as M1 and M2.ADB-BUTINACA mainly turned into its metabolites from debutylation(No.A1),formamide hydrolysis(No.A2),butyl carboxylation(No.A3)and

关 键 词：法医毒物学 MDMB-4en-PINACA ADB-BUTINACA 高效液相色谱-四极杆飞行时间质谱 体内代谢 代谢标记物 

分 类 号：DF795.1[医药卫生—法医学]