【摘要】 目的:以3H-1,2-二氢-2-(4-甲基苯胺基)甲基-1-吡咯里嗪酮(SFZ-47)为探针药物探索用鸡胚研究药物代谢的新方法。方法:SFZ-47(15mg)注入孵化10天的受精鸡蛋的卵清中,继续孵化72h,取尿囊液以XAD-2树脂处理,然后用液相色谱-电喷雾离子阱质谱进行分析。结果:三个代谢产物被鉴定,即4-(3H-1,2-二氢-1-吡咯里嗪酮-2-甲基胺基)苯甲醇(SFZ-47-OH),4-(3H-1,2-二氢-1-吡咯里嗪酮-2-甲基胺基)苯甲酸(SFZ-47-COOH)及其酯型葡萄糖苷酸结合物。结论:鸡胚可以进行药物的Ⅰ相和Ⅱ相代谢反应,有望成为药物代谢研究的一种新模型。更多还原

【Abstract】 AIM: To develop an alternative method for investigation of drug metabolism by fertilized chicken eggs using 3H-1,2-dihydro-2-(4-methyl-phenylamino) methyl-1-pyrrolizinone (SFZ-47) as a probe drug. METHODS: SFZ-47 (15mg) was injected into the albumen of eggs from standardized breed chickens previously incubated for 10d. After 72 h of further incubation, the allantoic liquid was subjected to solid phase extraction on XAD-2 columns and analyzed by liquid chromatography-electrospray ion trap mass spectrometry method. RESULTS: Three major metabolites were identified, namely 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methyl-amino) benzyl alcohol (SFZ-47-OH), 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methyl-amino)-benzoic acid (SFZ-47-COOH), and its glucuronide conjugates. The metabolic profile was little different from that previously found in rabbits and dogs. CONCLUSION: The result demonstrates the usefulness of the fertilized chicken egg as a convenient source of both phase Ⅰ and phase Ⅱ metabolites for further metabolism studies of SFZ-47.更多还原