N-oxidation: a possible route of tinidazole metabolism in man.
Treatment of tinidazole with a mixture of hydrogen peroxide and acetic acid, or liver homogenate preparations, yields the N-3 oxide. This was identified by thin-layer chromatographic analysis on silica gel G, Rf 0.6, using ethanol-chloroform-ammonia (50:49:1) as solvent, and by chemical reduction with sulphur dioxide. UV spectrophotometry and high performance liquid chromatography (HPLC) gave an RT of 0.55 min using Pye Unicam apparatus equipped with a UV detector at 330 nm, a reversed-phase RP 18 (10 microns) column which was 12.5 cm long, a mobile phase of methanol-0.005 M KH2PO4 (pH 4) (20:80, v/v) and a flow rate of 2 ml/min. In-vitro metabolic N-oxidation was achieved by incubating the parent drug, tinidazole, with rat liver homogenates fortified with cofactors at 37 degrees C. HPLC analysis of blood and urine samples from healthy volunteer subjects who took a single oral dose of tinidazole showed the presence of an in-vivo N-oxidation metabolite of the drug. The identical physico-chemical characteristics of the synthetic and biologically produced tinidazole N-oxide strongly suggest that tinidazole, a tertiary amine drug, undergoes metabolic N-oxidation.
Coker
H A
HA
Department of Pharmaceutical Chemistry, College of Medicine, University of Lagos, Nigeria.
Essien
E E
EE
Edoho
E J
EJ
D000328:Adult; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D009593:Nitroimidazoles / Q000378:metabolism*; D010084:Oxidation-Reduction; D010087:Oxides / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D014011:Tinidazole / Q000097:blood / Q000378:metabolism* / Q000652:urine
D009593:Nitroimidazoles; D010087:Oxides; D014011:Tinidazole