High-performance liquid chromatographic assay for the determination of p-(3,3-dimethyl-1-triazeno)benzoic acid in mouse plasma

J Chromatogr. 1985 Dec 13;345(2):323-31. doi: 10.1016/0378-4347(85)80169-9.

Abstract

A reproducible and sensitive method is described for assaying p-(3,3-dimethyl-1-triazeno)-benzoic acid (pCOOH-DMT) and for identifying the N-desmethyl metabolite, p-(3-methyl-1-triazeno)benzoic acid (pCOOH-MMT) using high-performance liquid chromatography. The method measures concentrations as low as 1.25 nmol/ml of plasma. Extraction efficiency of internal standard or of added triazenes averages 88% and the coefficient of variation of the method is less than 10%. pCOOH-DMT is stable at room temperature at pH 7.4, whereas pCOOH-MMT undergoes rapid decomposition (half-life 6 min). pCOOH-MMT is more stable in an albumin-containing solution or in plasma, but not in boiled 9000 g mouse liver. After 80 min incubation with a 9000 g mouse liver fraction and reduced nicotinamideadenine dinucleotide phosphate, only 24% pCOOH-DMT was metabolized. Plasma pharmacokinetic studies in mice treated with 200 mg/kg intraperitoneally showed that the potassium salt of pCOOH-DMT has a half-life of 67 min.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / blood*
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Drug Stability
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Kinetics
  • Liver / analysis
  • Mice
  • Mice, Inbred C57BL
  • Triazenes / blood*

Substances

  • Antineoplastic Agents
  • Triazenes
  • 1-(4-carboxyphenyl)-3,3-dimethyltriazene