2′-氯地西泮在大鼠体内分布及代谢降解规律研究

Pathway of Distribution and Metabolism of 2′-Diclazepam with Dosed Rats

目的研究2′-氯地西泮及其代谢物(地洛西泮、氯甲西泮、劳拉西泮)在大鼠体内分布及代谢规律,为2′-氯地西泮相关案件的检验提供实验数据。方法40只SD大鼠随机分为4组,禁食12h,按2.625mg/kg 2′-氯地西泮灌胃给药,第一组给药后不同时间点经大鼠尾静脉采血,第二组为采血空白对照组,第三组给药30min后处死,取心、肝、肺、肾、脑、睾丸,经乙酸乙酯液液萃取后用高效液相色谱-三重四极杆质谱检测2′-氯地西泮及代谢物含量,第四组为分布空白对照组。结果2′-氯地西泮进入体内后,迅速代谢分布,在20min内达到血液最高浓度。2′-氯地西泮及代谢物在各器官中的分布特点为:肝>脑>心脏>肾>睾丸>肺。结论经灌胃2′-氯地西泮进入大鼠体内后,监测2′-氯地西泮及其代谢物在大鼠体内的分布及降解规律可以为2′-氯地西泮相关案件的检验鉴定提供参考依据。

Objective To probe into the distribution and metabolism of 2′-diclazepam plus its metabolites(delorazepam,lormetazepam,lorazepam)with the dosed rats so as to provide reference data for the 2′-diclazepam-related cases.Methods 40 SD rats were randomly divided into 4 groups,leaving in fast for 12 hours,afterwards administered of 2′-diclazepam with two groups via gavage as per 2.625 mg/kg.Each rat of one group was collected of blood from the tail vein at different time after administration.Every member of another group was executed at 30 minutes elapsed from dosing,having its heart,liver,lung,kidney,brain and testicle collected to extract with ethyl acetate.The rest two groups were the blank controlling groups for the dosed groups,having the same destiny as their dosing counterpart.The bloods and extracts from the experimental rats were detected of 2′-diclazepam plus its metabolites with HPLC-MS/MS.Results 2′-diclazepam was rapidly distributed into rat tissues and metabolized,attaining its highest blood concentration within 20 minutes,demonstrating the discrepant distribution characteristics in various organs along with its metabolites as follows:liver>brain>heart>kidney>testicle>lung.Conclusion The pathway of distribution and metabolism of 2′-diclazepam plus its metabolites can provide reference with the gavage-dosed rats,bringing out the data valuable for identifi cation of 2′-diclazepam related cases.