用~2H-标记物和GC-MS分离鉴定联苯双酯在大鼠尿中的一个代谢产物  

USE OF ~2H-LABELED COMPOUND AND GC- MS IN THE ISOLATION AND IDENTIFICATION OF A METABOLITE OF BIPHENYLDIMETHYL- DICARBOXYLATE IN RAT URINE

作　　者：徐瑞明[1] 韩超[1] 谢晶曦[1] 宋振玉[1] 

机构地区：[1]中国医学科学院药物研究所,北京100050

出　　处：《药学学报》1990年第10期777-779,共3页Acta Pharmaceutica Sinica

摘　　要：联苯双酯(BDD)是人工合成的五味子丙素类似物,其化学结构为4,4′-二甲氧基-5,6,5′,6′-二次甲二氧基-2.2′-二甲氧羰基联苯,已用于迁、慢性肝炎的治疗。临床证明,该药降血清谷丙转氨酶的作用很强。为阐明其在体内的转化过程,并进一步研究其构效关系,我所曾用放射性同位素结合薄层层析对联苯双酯的代谢途径进行过研究。Dimethyl-4, 4′-dimethoxy-5, 6, 5′, 6′-dimethylenedioxybiphenyl-2, 2′-dicarboxylate (biphenyldimethyldicarboxylate; BDD), a synthetic compound, has been used in the treatment of chronic hepatitis with good results in reducing s-GPT. Previous work in our laboratory studied its metabolites using ~3H-labeled compound in combination with TLC and found that its main methabolic pathway is demethylation followed by conjugation with glucuronic acid. This paper reports the isolation and identification of a metabolite of BDD from rat urine using ~2H-labeled compound and GC-MS. Rats fasted for 12h were intragastrically given a mixture of ~2H-labeled (consisting of monodeutero-and dideutero-BDD in the ratio about 1:1.3)and non-labeled BDD 150mg/kg and placed in metabolism cages for urine collection. The 24h urine was filtered and extracted three times each with 5ml of methylenedichloride. The extracts were pooled and evaporated to dryness under reduced pressure at 35℃. The residue was redissolved in chloroform and subjected to GC-MS analysis. The mass spectrum (m/z: 404, 405, 406; 373, 374, 375; 345, 346, 347; 330, 331, 332; etc)indicates that the molecular ionic and fragment peaks of the metabolite all have 14 amu less than those of BDD. This means that the metabolite isolated is mono-O-demethylated BDD. The result confirmed our findings reported previously.

关 键 词：联苯双酯 代谢物 谷丙转氨酶 

分 类 号：R975.50[医药卫生—药品]