采用高效液相色谱法和毛细管电泳法对格鲁米特的立体选择性体外生物转化进行研究。
Investigation of the stereoselective in vitro biotransformation of glutethimide by high-performance liquid chromatography and capillary electrophoresis.
作者信息
Weinz C, Blaschke G, Schiebel H M
机构信息
Institute of Pharmaceutical Chemistry, University of Münster, Germany.
出版信息
J Chromatogr B Biomed Sci Appl. 1997 Mar 7;690(1-2):233-42. doi: 10.1016/s0378-4347(96)00390-8.
Due to our interest in drugs with a glutarimide structure, we reinvestigated the stereoselectivity of the in vitro biotransformation of the chiral hypnotic-sedative drug glutethimide. Glutethimide enantiomers were separated on a preparative scale by HPLC on cellulose tris(4-methylbenzoate) as chiral stationary phase. The enantiomeric purity was higher than 99%. A reversed-phase HPLC method was developed to determine the metabolites of glutethimide. After incubations with rat liver microsomes both enantiomers formed 5-hydroxyglutethimide as the main metabolite, as well as additional metabolites, of which some were formed stereoselectively. Mass spectrometry of the unknown metabolites indicated a hydroxylation in the ethyl side chain for two of the metabolites. A third metabolite was tentatively identified as desethylglutethimide.
由于我们对具有戊二酰亚胺结构的药物感兴趣，我们重新研究了手性催眠镇静药物格鲁米特体外生物转化的立体选择性。以三（4-甲基苯甲酸）纤维素为手性固定相，通过制备型高效液相色谱法对格鲁米特对映体进行了分离。对映体纯度高于99%。建立了一种反相高效液相色谱法来测定格鲁米特的代谢产物。与大鼠肝微粒体孵育后，两种对映体均形成5-羟基格鲁米特作为主要代谢产物，以及其他代谢产物，其中一些代谢产物是立体选择性形成的。未知代谢产物的质谱分析表明，其中两种代谢产物的乙基侧链发生了羟基化。第三种代谢产物初步鉴定为去乙基格鲁米特。
Zotero 插件