High pressure liquid chromatographic analysis of in vivo metabolites of N-(substituted phenyl)-N'-(1,3,5-trimethyl pyrazole-4-yl)thioureas in rats

Eur J Drug Metab Pharmacokinet. Oct-Dec 2007;32(4):225-32. doi: 10.1007/BF03191008.

Abstract

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in 5% gum arabic and administered 100 mg/kg intraperitoneally (i.p.) in a volume of 0.1 ml/100 g. Blood samples were withdrawn before and at 30 min, 1, 2, 4, 8, 12 and 24 h post-dose.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.

MeSH terms

  • Animals
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Injections, Intraperitoneal
  • Male
  • Pyrazoles / metabolism*
  • Pyrazoles / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Spectrophotometry, Ultraviolet
  • Thiourea / analogs & derivatives*
  • Thiourea / metabolism*
  • Thiourea / pharmacokinetics

Substances

  • Pyrazoles
  • Thiourea