高效快速灵敏的药物代谢方法研究

The biotransformation of several drug candidates including the antianxiety agent AF-5, anti-cerebral ischemia agent 6-amino butyl phthalide (ABP) and the antitumor agent R9158 has been studied by using the methods of mass spectrometry such as MS/MS, LC-MS, LC-MS/MS and GC-MS. The structures of the metabolites have been characterized by LC-MS/MS and GC-MS. The metabolic pathways of the compounds have been investigated by profiling the metabolites in vivo and in vitro. We have also studied the metabolism of some active components in traditional Chinese medicine. Furthermore, a new technique involving rapid sampling of in real-time was developed by using a combination of microdialysis and liquid chromatography-tandem mass spectrometry (LC-MS/MS), the concentrations of ABP and its metabolites in rat's cerebrospinal fluid (CSF) were determined by this method. The results of this project proved that the techniques which have been applied in these studies are not only highly sensitive and specific but also have great value and excellent perspective in the study of drug metabolism and pharmacokinetics.

对正在研制的抗肿瘤创新药（R9158）进行系统的体内外代谢研究，并探索其活性代谢产物Ｍ崩酶叻直妗⒏吡槊舻拇势准捌溆肷椎牧眉际鮈C(GC) -MS/MS，通过对R9158驼谘兄浦械募钢稚窬低承乱┑拇徊镅芯浚剿髦苯硬舛ǎㄎ⒘浚┐换旌衔锖筒晃榷ㄖ屑浯晃锏姆治龇椒ǎ⒔岷显淮煌晟埔┪锏拇谎芯浚乱┑慕徊窖兄坪涂⑻峁├砺垡谰荨Ｍü鞠钅康难芯浚⑵鹗屎隙嘀忠┪锏奶迥谕獯晃锟焖佟⒘槊簟⒆既返姆治龇椒ê脱芯客揪丁Ｆ淠康奈臁⒏娴卣莆找┪锎恍畔ⅲ涌齑葱乱┪锏难芯靠傩戮置妗