High pressure liquid chromatographic analysis of in vivo metabolites of N-(substituted phenyl)-N'-(1,3,5-trimethyl pyrazole-4-yl)thioureas in rats.
The aim of this study was to investigate the in vivo metabolism of N-(substituted phenyl)-N'-(1,3,5-trimethylpyrazole-4-yl)thioureas (substrate) as model compounds in rats via HPLC. The substrates, N-(4-fluoro/chlorophenyl)-N'-(1,3,5-trimethylpyrazole-4-yl)thioureas (T2 and T3), and their possible metabolites were synthesized and the structures of the compounds were elucidated both by spectral and elemental analysis. Substrates were dissolved in 5% gum arabic and administered 100 mg/kg intraperitoneally (i.p.) in a volume of 0.1 ml/100 g. Blood samples were withdrawn before and at 30 min, 1, 2, 4, 8, 12 and 24 h post-dose. Chromatographic separation of the substrate and its metabolites was performed using a Hichrom chromasil C18 column (150 mm x 4.6 mm i.d., 5 microm particle size). The optimal composition of the mobile phase was achieved by using different mixtures of pure methanol and water. From the biotransformation of these thiourea compounds, N-dealkylation metabolites N-(4-fluoro/chloro-phenyl)-N'-(3,5-dimethylpyrazole-4-yl)thioureas (TI and T4) were identified together with unchanged substrate (T2 and T3) in the plasma by comparing them to reference standards via HPLC UV/DAD.
Kocyigit-Kaymakcioglu
Bedia
B
Marmara University, Faculty of Pharmacy, Departments of Pharmaceutical Chemistry, Istanbul, Turkey.
Yilmaz
Ufuk
U
Aricioglu
Feyza
F
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D007274:Injections, Intraperitoneal; D008297:Male; D011720:Pyrazoles / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D013890:Thiourea / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics
D011720:Pyrazoles; D013890:Thiourea