氟胺酮及其代谢物去甲氟胺酮在大鼠体内分布及代谢降解规律研究  

Distribution and Metabolic Pathway of F-ketamine and Its Metabolite F-norketamine in Rats

作　　者：蔡玉刚 米兰[2] 吴永富 邹多生[2] 黄叙金 王燕军[2] 代勇[3] CAI Yugang;MI Lan;WU Yongfu;ZOU Duosheng;HUANG Xujin;WANG Yanjun;DAI Yong(Institute of Criminal Science and Technology,Luzhou Public Security Bureau,Luzhou 646000,Sichuan,China;Criminal Investigation Division,Sichuan Provincial Public Security Department,Chengdu 610041,China;Sichuan Police College,Luzhou 646000,Sichuan,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]四川省公安厅刑侦局,成都610041 [3]四川警察学院,四川泸州646000

出　　处：《刑事技术》2022年第4期388-394,共7页Forensic Science and Technology

基　　金：四川省省级大学生创新创业训练项目(S202012212005);四川省公安厅厅级科研创新项目(2020SCYY01)。

摘　　要：目的建立生物样品中氟胺酮及其代谢物去甲氟胺酮的检测方法,研究氟胺酮及去甲氟胺酮在大鼠体内降解规律及脏器分布特点。方法利用高效液相色谱-三重四极杆质谱(HPLC-MS/MS)检测生物样品中氟胺酮及去甲氟胺酮;40只SD大鼠随机分为4组,禁食12 h,按0.045 mg/kg氟胺酮灌胃给药,第一组给药后不同时间点采集大鼠尾静脉血,第二组作为血液对照组;第三组给药1 h后处死,取血、心、肝、肺、肾、脑、脾、肌肉,经快速溶剂萃取提取后检测氟胺酮和去甲氟胺酮含量,第四组作为内脏空白对照组。结果建立了生物检材中氟胺酮及代谢物去甲氟胺酮的HPLC-MS/MS检验方法,该方法氟胺酮及去甲氟胺酮在0.02~200 ng/mL(ng/g)浓度范围内线性关系良好,相关系数大于0.9922,方法回收率大于82.06%。氟胺酮进入体内后,迅速分布代谢,在0.5 h内达到血液最高浓度。氟胺酮在体内的分布特点为:血>肝>脾>肾>肌肉>脑>肺>心脏,去甲氟胺酮的分布特点为:血>肝>肾>肺>脾>肌肉>心脏>脑。结论所建立的方法速度快、操作简单、检出限低、回收率高、重现性好,适用于生物样品中氟胺酮及去甲氟胺酮的检验。经灌胃氟胺酮进入大鼠体内后,监测氟胺酮及去甲氟胺酮在大鼠体内的分布及降解规律可为体内氟胺酮检验提供科学依据。Objective To establish a method for determination of F-ketamine and its metabolite F-norketamine in biological evidential samples through exploring into the degradation pathway and organ distribution of the two chemicals in rats.Methods 40 SD rats were randomly divided into 4 groups and fasted for 12 hours,having each individual of one group administered with F-ketamine by gavage as per 0.045 mg/kg plus another group being taken as the blank control.Rats of the two groups were collected of their respective blood from tail vein at different time points after administration.Rats of the third group were executed to death at 1h after drug administration,with their blood,heart,liver,lung,kidney,brain,spleen and muscle being collected and extracted with rapid solvent extraction.The last remaining group was the blank control to third group.F-ketamine and F-norketamine were detected of their contents with HPLC-MS/MS.Results The linear range of F-ketamine and F-norketamine was both 0.02-200 ng/mL(ng/g),with the correlation coeffi cient being greater than 0.9922 and the recovery more than 82.06%.F-ketamine was found of rapid metabolizing and distributing in rats,having reached the highest blood concentration within 0.5 h.The organ-characteristic distribution of F-ketamine in rats was as follows:blood>liver>spleen>kidney>muscle>brain>lung>heart,with that of F-norketamine being as blood>liver>kidney>lung>spleen>muscle>heart>brain.Conclusions The method is advantageous of high speed,simple operation,low detection limit,high recovery rate and good reproducibility,suitable for the determination of F-ketamine and F-norketamine in biological evidential samples.The distribution and degradation pathway of F-ketamine and F-norketamine in the rats undergone with gavage of F-ketamine can provide scientifi c basis for in vivo test and process analysis of F-ketamine.

关 键 词：氟胺酮 去甲氟胺酮 快速溶剂萃取 高效液相色谱-三重四极杆质谱 体内分布 代谢降解 

分 类 号：DF795.1[医药卫生—法医学]