【作者】 宫爱申； 陈笑艳； 邓泮； 钟大放；

【Author】 GONG Ai-shen~(1,2),CHEN Xiao-yan~1,DENG Pan~1,ZHONG Da-fang~1 1 Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;2 Shanghai Hengrui Pharmaceutical Co.,Ltd., Shanghai 200245,China

【机构】 中国科学院上海药物研究所； 上海恒瑞医药有限公司；

【摘要】 目的:研究酪氨酸激酶抑制剂抗肿瘤新药甲磺酸氟马替尼在慢性粒细胞白血病人体内的主要代谢产物。方法:受试者口服甲磺酸氟马替尼后的血浆、尿及粪样分别经固相萃取和沉淀蛋白预处理后,采用UPLC/Q-TOF质谱进行分析,并与合成的代谢物对照品对比,鉴定代谢物的结构。结果:受试者口服甲磺酸氟马替尼后,血浆、尿和粪样中共检测到代谢物34种,包括Ⅰ相代谢物25种和Ⅱ相代谢物9种。结论:氟马替尼在人体内主要代谢途径为N-去甲基化、羟基化、N-氧化、酰胺水解,乙酰化及葡萄糖醛酸化等更多还原

【Abstract】 AIM:To identify primary metabolites of flumatinib mesylate in chronic myelocytic leukemia patients.METHODS:Plasma, urine and feces were purified through solid-phase extraction cartridge or protein precipitation.Data collection was done by UPLC/QTOF MS,and metabolite structure was characterized by comparison with reference compounds.RESULTS:After oral administration of flumatinib to volunteers,34 metabolites including 25 phaseⅠand 9 phaseⅡmetabolites were detected in plasma,urine and feces.CONCLUSION: The main metabolism routes of flumatinib in human were N-desmethylation,hydroxylation,N-oxidation,amide hydrolysis, acetylation and glucuronate conjugation.更多还原