IDENTIFICATION AND CHARACTERIZATION OF LIMONENE METABOLITES IN PATIENTS WITH ADVANCED CANCER BY LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY

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 reverse d-phase HPLC-atmospheric pressure chemical ionization and electrospray ionization MS, The drug underwent rapid conversion to hydroxylated an d carboxylated derivatives. Characterization and structural elucidatio n of the metabolites were achieved by LC/MS and NMR. Five major metabo lites were detected in the plasma extracts, namely limonene-1,2-diol, limonene-8,9-diol, perillic acid, an isomer of perillic acid, and dihy droperillic acid, Urinary metabolites comprised the glucuronides of th e two isomers of perillic acid, dihydroperillic acid, limonene-8,9-dio l, and a monohydroxylated limonene.