Xu R M, Han C, Xie J X, Song Z Y
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing.
Yao Xue Xue Bao. 1990;25(10):777-9.
Dimethyl-4, 4'-dimethoxy-5, 6, 5', 6'-dimethylenedioxy-biphenyl-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 metabolic 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 12 h 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 150 mg/kg and placed in metabolism cages for urine collection. The 24 h urine was filtered and extracted three times each with 5 ml of methylenedichloride. The extracts were pooled and evaporated to dryness under reduced pressure at 35 degrees C. 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.
4,4'-二甲氧基-5,6,5',6'-二亚甲基二氧基联苯-2,2'-二甲酸二甲酯（联苯二甲酸二甲酯；BDD），一种合成化合物，已被用于治疗慢性肝炎，在降低血清谷丙转氨酶方面取得了良好效果。我们实验室之前的工作使用3H标记的化合物结合薄层色谱法研究了其代谢产物，发现其主要代谢途径是去甲基化，然后与葡萄糖醛酸结合。本文报道了使用2H标记的化合物和气相色谱-质谱联用技术从大鼠尿液中分离和鉴定BDD的一种代谢产物。禁食12小时的大鼠经胃内给予2H标记（由单氘代和双氘代BDD按约1:1.3的比例组成）和未标记的BDD混合物150mg/kg，并置于代谢笼中收集尿液。将24小时尿液过滤，每次用5ml二氯甲烷萃取三次。合并萃取液，在35℃减压下蒸发至干。残余物重新溶解于氯仿中，进行气相色谱-质谱分析。质谱图（m/z：404、405、406；373、374、375；345、346、347；330、331、332等）表明，该代谢产物的分子离子峰和碎片峰均比BDD的相应峰少14amu。这意味着分离得到的代谢产物是单-O-去甲基化的BDD。该结果证实了我们之前报道的发现。
