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 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.
Poon
G K
GK
Cancer Research Campaign Centre for Cancer Therapeutics, Charing Cross Hospital.
Vigushin
D
D
Griggs
L J
LJ
Rowlands
M G
MG
Coombes
R C
RC
Jarman
M
M
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
D000972:Antineoplastic Agents, Phytogenic; D053138:Cyclohexenes; D013729:Terpenes; D000077222:Limonene; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase