title: Identification and characterization of limonene metabolites in patients with advanced cancer by liquid chromatography/mass spectrometry.
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.
authors.affiliation: Cancer Research Campaign Centre for Cancer Therapeutics, Charing Cross Hospital.
authors.forename: G K
authors.initials: GK
authors.lastname: Poon
authors.forename: D
authors.initials: D
authors.lastname: Vigushin
authors.forename: L J
authors.initials: LJ
authors.lastname: Griggs
authors.forename: M G
authors.initials: MG
authors.lastname: Rowlands
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
authors.forename: M
authors.initials: M
authors.lastname: Jarman
mesh_terms: D000328:Adult; D000368:Aged; D019883:Alkyl and Aryl Transferases; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000378:metabolism* / Q000652:urine; D001943:Breast Neoplasms / Q000378:metabolism*; D002853:Chromatography, Liquid; D015179:Colorectal Neoplasms / Q000378:metabolism*; D053138:Cyclohexenes; D051231:Farnesyltranstransferase; D005260:Female; D006801:Humans; D000077222:Limonene; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015394:Molecular Structure; D013729:Terpenes / Q000097:blood / Q000378:metabolism* / Q000652:urine; D014166:Transferases / Q000037:antagonists & inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053138:Cyclohexenes; D013729:Terpenes; D000077222:Limonene; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase