手性毛细管气相色谱法测定人尿中美芬妥英光学异构体含量的方法学研究  

A CHIRAL CAPILLARY GAS CHROMATOGRAPHIC METHOD FOR DIRECT DETERMINATION OF ENANTIOMERS OF MEPHENYTOIN IN HUMAN URINE

作　　者：匡唐永[1] 张家美[2] 邹安庆[2] 楼雅卿[1] 

机构地区：[1]北京医科大学药理教研室 [2]天然药物及仿生药物国家重点实验室,北京100083

出　　处：《药学学报》1993年第4期307-311,共5页Acta Pharmaceutica Sinica

摘　　要：抗癫痫药美芬妥英(mephenytion,MP)是乙内酰脲的5位碳上被乙基和苯环取代的化合物。其中乙内酰脲环上的5位碳不对称,有旋光性。美芬妥英是由S-和R-两种对映体组成的混旋体。在人体内,主要通过两条途径进行代谢,并存在立体异构选择性。即R-MP主要通过脱甲基生成5-苯基-5-乙基乙内酰脲(norvanol,PEH);S-MP主要通过芳香基对位羟化生成3-甲基-5-(4′-羟基苯基)-5-乙基乙内酰脲(4′-OH-MP)(图1),小部分S-MP经去甲基生成S-PEH。A gas chromatographic method equipped with nitrogen-phosphorus detector was developed for the determination of the S-and R-enantiomers of the anticonvulsant, mephenytoin (MP) in human urine. Dichioromethane (4 ml) was added to 1 ml urine, the mixture was shaken and centrifuged. The organic phase was transferred to another tube and blown to dryness under nitrogen on water bath (37℃). The residue was dissolved in 10 μl ethylacetate and 1～2 μl was injected into the GC. Our results showed that direct enantiomeric separation of mephenytoin was obtained by using a chiral capillary column, the retention times for S- and R-mephenytoin were 25. 5 and 26. 2 min respectively, with a detection limit less than 50 ng/ml of mephenytoin. Similar linear and reproducible standard curves were obtained over the concentration range of 53.2 to 2128. 0 ng/ml (for S-MP, r=0. 9914±0. 0070, n=6; and for R-MP, r=0. 9939±0. 0070, n=6), and the mean recoveries of S-and R-MP were 95. 4% and 95. 8% respectively. The within--day relative standard deviations were less than 8. 8% for both S- and R-MP, and that of between--days were less than 14.3%. There was a good reproducibility of the urine S/R mephenytoin determined in China and in Sweden by using similar method in 107 Chinese volunteers after a single oral dose of 100 mg racemic mephenytoin (r=0. 9091, P<0. 001).

关 键 词：美芬妥英 尿 光学异构体 色谱法 

分 类 号：R914.1[医药卫生—药物化学]