摘要
目的研究新化合物4-甲基哌嗪-1-二硫代甲酸-(3-氰基-3,3-二苯基)丙酯盐酸盐(TM208)在大鼠体内的主要代谢产物。方法大鼠ig TM208 500 mg.kg-1后,收集粪样、尿样和血样,用液相色谱-电喷雾离子阱质谱法测定。根据TM208及其代谢产物的色谱保留时间和电喷雾离子阱质谱(ESI-ITMSn)电离规律及生物体内药物代谢转化规律,推导代谢物的结构。结果在粪样中发现8种I相代谢产物,在尿样和血样中发现5种I相代谢产物,未发现II相代谢产物。结论本法操作简便、快速、灵敏度高、专属性强,是一种研究TM208体内代谢产物的有效方法。
Aim To identify the main metabolites of hydrochloride 4-methyl-piperazine-1- carbodithiocacid 3-cyano-3,3-diphenyl-propyl ester （TM208） in rats. Methods Rat feces, urine and plasma samples were collected after ig 500 mg·kg^-1 TM208, then the samples were extracted and concentrated using ethyl acetate. The treated samples were analyzed by HPLC-ESI/ITMS^n. The structures of metabolites were elucidated according to the rules of drug metabolism and disposition in vivo and the characteristic fragmentation behaviors of TM208 in ESI-ITMS^n. Results Eight phase Ⅰ metabolites were identified existing in rat feces, five of them were also found in rat urine and plasma, but no phase Ⅱ metabolite was found. Conclusion The HPLC-ESI/ITMS^n method is rapid, highly sensitive and specific and it is suitable for the identification of TM208 and its metabolites in rats.
出处
《药学学报》
CAS
CSCD
北大核心
2006年第11期1084-1089,共6页
Acta Pharmaceutica Sinica
基金
国家高技术研究发展计划(863计划)资助项目(2004AA2Z3783)
