Characterisation of urinary metabolites of temozolomide in humans and mice and evaluation of their cytotoxicity

Cancer Chemother Pharmacol. 1990;26(6):429-36. doi: 10.1007/BF02994094.


The experimental antineoplastic agent temozolomide was not metabolised in vitro at a measurable rate by mouse liver fractions. In contrast, the temozolomide analogue 3-methylbenzotriazinone was metabolically N-demethylated by hepatic microsomes to yield benzotriazinone. The major route of excretion of [14C]-labelled temozolomide in mice was via the kidneys. An acidic metabolite of temozolomide, probably a conjugate, was found in the urine of mice, but its identity could not be established unambiguously. Spectroscopic analysis and chemical tests revealed that it possesses an intact NNN-linkage. Another metabolite was found in the urine of patients but not of mice. This metabolite was identified as the 8-carboxylic acid derivative of temozolomide. Unlike the unknown species, this metabolite was cytotoxic against TLX5 lymphoma cells in vitro.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity
  • Antineoplastic Agents / urine*
  • Chromatography, High Pressure Liquid
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / toxicity
  • Dacarbazine / urine
  • Drug Evaluation
  • Drug Screening Assays, Antitumor
  • Humans
  • In Vitro Techniques
  • Lymphoma / drug therapy
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Microsomes, Liver / enzymology
  • Oxidation-Reduction
  • Temozolomide
  • Thymus Neoplasms / drug therapy
  • Triazines / pharmacokinetics
  • Tumor Cells, Cultured / drug effects


  • Antineoplastic Agents
  • Triazines
  • 3-methylbenzotriazin-4-one
  • Dacarbazine
  • Temozolomide