2′-氯地西泮在大鼠体内分布及代谢降解规律研究

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。

Psychoactive Chemical Constituents of Carissa edulis (Forssk.) Vahl Roots and Its Safety Limits in Folk Treatment: Benzodiazepines Analogous

Carissa edulis Vahl is well known in Sudanese herbal medicine,commonly used for treatment of epilepsy,headache,chest pains,rheumatism,skin lesions,mania and other psychoactive diseases.The investigations of the safety use for psychoactive purposes in Sudanese healing traditions and identifying secondary metabolites of the plant extracts are the key steps towards determination of appropriate medicinal doses.Therefore,one of the chemical constituents was isolated and structurally identified by 1H-NMR and LC-MS.With the aim of evaluating Carissa edulis folk random uses,the isolated compound was compared with reference artificial drugs Lormetazepam,a potentially toxic compound.Structure investigations confirm that the isolated product was benzodiazepines analogous 7-chloro 1,4-benzodiazepine-2-ones.It is important to know the potential toxicity of certain plant in order to assess the therapeutic effect of it,as these are slight distinctions between the medicinal and toxic doses.In general the results obtained justify the use of the roots of Carissa edulis in traditional medicine for the treatment of some psychiatric diseases.

氯甲西泮的合成工艺研究

目的对氯甲西泮的合成工艺进行研究。方法以2-氨基-2',5-双氯二苯甲酮为原料,经过成肟反应、扩环反应、甲基化反应、乙酰化反应、碱解反应,再通过两次乙醇精制得到氯甲西泮成品。结果与结论目标化合物的结构经核磁共振氢谱(~1H-NMR)、核磁共振碳谱(^(13)C-NMR)、质谱(MS)等确定,总收率达到20%。该合成工艺原料易得,操作简单,各步中间体质量收率稳定,适用于大工业生产。