新型抗炎镇痛剂SFZ-47在家兔体内羟基化及其结合型代谢产物的鉴定  

IDENTIFICATION OF HYDROXYLATED METABOLITE OF SFZ 47, A NOVEL ANTI INFLAMMATORY AND ANALGESIC AGENT, AND ITS CONJUGATES IN RABBITS

作　　者：顾景凯[1] 钟大放[2] 郭继芬[2] 周慧[1] 沈家骢[1] 

机构地区：[1]吉林大学生命科学学院,长春130023 [2]沈阳药科大学药物代谢与药物动力学实验室,沈阳110015

出　　处：《药学学报》2000年第3期181-184,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金!资助项目 (3962 50 2 5)

摘　　要：目的 :鉴定新型抗炎镇痛剂SFZ 4 7[3H 1,2 二氢 2 ( 4 甲基苯胺基 )甲基 1 吡咯里嗪酮 ]在家兔体内的羟基化及其结合型代谢产物。方法 :选择 4只健康家兔单剂量口服 10 0mgSFZ 4 7,收集 0～ 10h的尿样。将未经或经过 β D 葡萄糖苷酸酶 /硫酸酯酶水解的尿样以Sep PakC18固相萃取柱纯化后 ,采用LC/MSn 方法对尿中推测的代谢物分别进行选择离子监测 (SIM )和多级全扫描质谱 (MSn)分析。结果 :在尿中首次检测到SFZ 4 7羟基化及其 β D 葡糖苷酸与硫酸结合型代谢物。结论 :SFZ 4 7在家兔体内主要代谢途径应为苯环上的甲基先氧化成羟甲基和羧基 ,再分别与 β DAIM: To identify the metabolite of 3H 1,2 dihydro 2 (4 methyl phenylamino) methyl 1 pyrrolizinone(SFZ 47), a novel anti inflammatory and analgesic agent in rabbits. METHODS: Urine samples from 0 to 12 h were collected after single oral dose of 100 mg SFZ 47 to each of four rabbits. The urine samples with or without hydrolysis by β glucuronidase/sulphatase were purified by SPE column (Sep Pak C 18 ) and analyzed with LC/MS n for potential metabolites. RESULTS: Hydroxylated metabolite of SFZ 47 and its conjugates of glucuronide and sulfate were first identified either by directly comparing the observed mass spectra and the chromatographic retention time with authentic substance or by the diagnostic ions in full scan MS n ( n =2,3) mode. CONCLUSION: According to the experimental results in this study, the major metabolic pathway of SFZ 47 in rabbits should be that the methyl group of SFZ 47 was oxidized to hydroxymethyl and then to carboxyl group, followed by conjugation with β glucuronic acid or sulfuric acid.

关 键 词：抗炎镇痛剂 SFZ-47 羟基化 代谢物 家兔 

分 类 号：R971.1[医药卫生—药品]