丙泊酚及其代谢物在大鼠体内的动态分布

Dynamic distribution of Propofol and its metabolites in Rats

目的研究丙泊酚及其代谢物(4-羟基丙泊酚和葡萄糖醛酸丙泊酚)在大鼠体内的动态分布规律,为丙泊酚麻醉相关的死亡案件法医学鉴定提供实验依据。方法 72只SD大鼠随机分为12组,禁食12h,经尾静脉注射12.6mg/kg丙泊酚,给药后不同时间点处死,取心、肝、肺、肾、脑、肌肉、睾丸、静脉血,检材分为两份,一份经环己烷及乙腈液液萃取法提取后,用气相色谱-串联质谱仪检测丙泊酚含量,并用高效液相色谱-串联质谱仪检测PG含量,另一份检材经乙腈液液提取后经MSTFA衍生化,用气相色谱-串联质谱仪检测4-羟基丙泊酚含量。结果丙泊酚经大鼠尾静脉进入体内,迅速向各组织器官内分布。由数据可看出丙泊酚在体内各组织消除迅速,并于30min后趋于平稳。丙泊酚在大鼠肝、肾、脑中分布较多,PG在大鼠中主要分布在肝脏,4-羟基丙泊酚在大鼠肝脏、肾脏、肺脏分布较多。结论经尾静脉注射丙泊酚后大鼠体内丙泊酚及其代谢物的动态分布规律可以为丙泊酚麻醉相关的死亡案件的法医学鉴定提供实验依据。

Objective The dynamic distribution of propofol and its metabolites in rats were studied to provide evidence for forensic cases of death that related to propofol-anesthetization.Methods 72 SD rats were randomly divided into 12 groups and fasting for 12 hours,then 12.6 mg/Kg propofol were given to the 72 rats respectively by intravenous injection and were executed.The hearts,livers,lungs,kidneys,brains,muscle,testicles,venous blood were collected at different time points.The samples were divided into two parts,one part was extracted by liquid-liquid extraction with cyclohexane and acetonitrile,and then propofol was detected by GC-MS/MS,PG was detected by LC-MS/MS.Another part was extracted by Liquidliquid extraction with acetonitrile and cyclohexane then was derived by MSTFA.After that,4-hydroxy propofol was detected by GC-MS/MS.Results Propofol distributed quickly to tissues and organs.According to data,propofol in rats decreased quickly,and tended to be stable after 30 min.Propofol distributed most in liver,kidney,brain.PG distributed most in liver.4-hydoxy propofol distributed most in the livers,kidneys and lungs.Conclusion The dynamic distribution of propofol and its metabolites can provide evidence for forensic identification of death cases related to propofolintravenous injection.