Identification and characterization of limonene metabolites in patients with advanced cancer by liquid chromatography/mass spectrometry

Drug Metab Dispos. 1996 May;24(5):565-71.

Abstract

Limonene is a farnesyl transferase inhibitor that has shown antitumor properties. The drug had been given orally to cancer patients. Plasma and urine samples collected from the patients were examined by reversed-phase HPLC-atmospheric pressure chemical ionization and electrospray ionization MS. The drug underwent rapid conversion to hydroxylated and carboxylated derivatives. Characterization and structural elucidation of the metabolites were achieved by LC/MS and NMR. Five major metabolites were detected in the plasma extracts, namely limonene-1,2-diol, limonene-8,9-diol, perillic acid, an isomer of perillic acid, and dihydroperillic acid. Urinary metabolites comprised the glucuronides of the two isomers of perillic acid, dihydroperillic acid, limonene-8,9-diol, and a monohydroxylated limonene.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alkyl and Aryl Transferases*
  • Antineoplastic Agents, Phytogenic / blood
  • Antineoplastic Agents, Phytogenic / metabolism*
  • Antineoplastic Agents, Phytogenic / urine
  • Breast Neoplasms / metabolism*
  • Chromatography, Liquid
  • Colorectal Neoplasms / metabolism*
  • Cyclohexenes
  • Farnesyltranstransferase
  • Female
  • Humans
  • Limonene
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Molecular Structure
  • Terpenes / blood
  • Terpenes / metabolism*
  • Terpenes / urine
  • Transferases / antagonists & inhibitors

Substances

  • Antineoplastic Agents, Phytogenic
  • Cyclohexenes
  • Terpenes
  • Limonene
  • Transferases
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase