新抗炎镇痛剂SFZ-47在家兔体内主要代谢产物的分离与鉴定  

ISOLATION AND IDENTIFICATION OF A MAJOR METABOLITE OF SFZ-47 IN THE RABBIT URINE

作　　者：董庆光[1] 顾景凯[1] 钟大放[2] 初大丰[1] 孙璐[2] 

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

出　　处：《药学学报》2002年第2期141-143,共3页Acta Pharmaceutica Sinica

基　　金：国家自然科学重点 (3 993 0 180 );面上项目基金资助(3 0 0 70 879)

摘　　要：目的　建立家兔尿液中新抗炎镇痛剂SFZ 4 7一葡糖苷酸代谢物的分离纯化方法 ,并对其结构进行确证。方法　健康家兔 ,单剂量igSFZ 4 72 0 0mg,收集 0～ 2 4h尿样 ;将尿样经冷冻干燥和甲醇溶解后 ,用半制备型HPLC对粗提物中该代谢产物进行分离与制备 ,以ESI MSn 和1 HNMR技术对其进行结构确证。结果　首次直接证明该代谢物为SFZ 4 7羧基衍生物的葡糖苷酸结合物。结论　本法操作简便 ,分离效果好 ,可用于SFZ 4AIM To isolate and identify a glucuronide metabolite of SFZ 47 [3H 1,2 dihydro 2 (4 methyl phenylamino)methyl 1 pyrrolizinone], which is difficult to synthesize because it undergoes hydrolysis and intramolecular acyl migration at physiological pH, in rabbit urine. METHODS Two rabbits were ig 200 mg doses of SFZ 47. Urine was collected for 24 h, adjusted to pH 4 0 with acetic acid and lyophilized. The residues were reconstituted in 25 mL methanol and centrifuged at 5 000 r·min -1 for 10 min. The supernatant was filtered (0 45 μm) and then isolated with semi preparative reversed phase HPLC. The eluent collected from individual peaks was evaporated by rotary evaporation and freeze drying. Compounds were then identified with electrospray ion trap mass spectrometry and 1HNMR spectroscopy. RESULTS The 1HNMR and ESI MS n results indicate that the metabolite is the 1 O acyl β D glucuronide conjugate of 4 (3H 1,2 dihydro 1 pyrrolizinone 2 methylamino) benzoic acid. CONCLUSION This method was shown to be rapid and simple and gave excellent resolution from endogenous constituents in urine, and it is suitable for preparation of the glucuronide metabolites of SFZ 47 and its analogues.

关 键 词：SFZ-47 抗炎镇痛剂 新药 动物实验 分离 鉴定 葡糖苷酸 HPLC 电喷雾离子阱质谱法 

分 类 号：R971.1[医药卫生—药品] R962[医药卫生—药学]