Chromatographic and spectroscopic characterization of sulphur-bound dimetridazole and ranidazole derivatives.
The 5-nitroimidazoles, dimetridazole and ronidazole, two important veterinary drugs, were reacted under reductive conditions with the sulfhydryl-containing substrates cysteine and glutathione to yield 5-amino-4-S-substituted imidazoles. After purification by reversed-phase liquid chromatography (RP-LC), the four adducts were characterized by RP-LC with photodiode array detection using conditions where their parent drugs were not eluted from the column. Structural identification was conducted by spectroscopic techniques, mainly 1-dimensional and 2-dimensional NMR. While the dimetridazole adducts were found to be monosubstituted at the C-4 position, the two ronidazole products contained two units of the sulfhydryl substrate, located at the C-4 and C-6 positions.
Girard
M
M
Bureau of Drug Research, Health and Welfare Canada, Ottawa, Ontario.
Carignan
G
G
Mousseau
N
N
Dawson
B A
BA
D002853:Chromatography, Liquid; D003545:Cysteine / Q000032:analysis; D004131:Dimetridazole / Q000031:analogs & derivatives / Q000032:analysis*; D005978:Glutathione / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D012385:Ronidazole / Q000031:analogs & derivatives / Q000032:analysis*; D013056:Spectrophotometry, Ultraviolet; D013438:Sulfhydryl Compounds / Q000032:analysis
D013438:Sulfhydryl Compounds; D012385:Ronidazole; D005978:Glutathione; D004131:Dimetridazole; D003545:Cysteine