医薬品の体内変化に関する研究(第6報) : スルフイソメゾールの新体内変化物について その2

抄録

Biological change of sulfisomezole (N¹-(5-methyl-3-isoxazole) sulfanilamide) in the human body was examined. Human urine after administration of sulfisomezole was mixed with activated charcoal, the adsorbed charcoal was eluted with ammonia-alkaline solvent, and the solvent was concentrated in a reduced pressure. The concentrated solution was passed through a column of Dowex 50-X8, the column was eluted with water, and the aqueous eluate was passed through a column of Amberlite IRA-68. The column was eluted with diluted ammonia water, the precipitate formed by the addition of lead acetate was removed, and the substance precipitated by basic lead acetate was collected by filtration. The precipitate was dissolved in ammonium sulfate solution and filtered, and the filtrate was passed through SE-Sephadex C-25 medium. The solution was neutralized with 0.1N sodium hydrogencarbonate and submitted to paper partition chromatography. The exlracted solution was passed through columns of Amberlite IRP-64 and Dowex 4, and evaporation of the effluent afforded a crystalline residue. Hydrolysis of this crystalline residue afforded sulfisomezole and glucuronic acid in 1 : 1 molar ratio. Their binding locus was examined by the comparison of Rf values of the conjugate in paper partition chromatography developed with neutral and alkaline media, study of its solubility, and the absorption bands of SO₂ at 1138 and 971cm^-1 in the infrared spectrum of These evidences indicated that this compound is an imide-type conjugate the glucuronic acid attached to the nitrogen in the isoxazole ring. Therefore, the biological product of sulfisomezole is a sodium sulfisomezole 2'-glucosiduronate containing 1 mole of water of crystallization.