Quantification of 1,8-cineole and of its metabolites in humans using stable isotope dilution assays.
The metabolism of 1,8-cineole after ingestion of sage tea was studied. After application of the tea, the metabolites 2-hydroxy-1,8-cineole, 3-hydroxy-1,8-cineole, 9-hydroxy-1,8-cineole and, for the first time in humans, 7-hydroxy-1,8-cineole were identified in plasma and urine of one volunteer. For quantitation of these metabolites and the parent compound, stable isotope dilution assays were developed after synthesis of [(2)H(3)]-1,8-cineole, [9/10-(2)H(3)]-2-hydroxy-1,8-cineole and [(13)C,(2)H(2)]-9-hydroxy-1,8-cineole as internal standards. Using these standards, we quantified 1,8-cineole by solid phase microextraction GC-MS and the hydroxyl-1,8-cineoles by LC-MS/MS after deconjugation in blood and urine of the volunteer. After consumption of 1.02 mg 1,8-cineole (19 μg/kg bw), the hydroxycineoles along with their parent compound were detectable in the blood plasma of the volunteer under study after liberation from their glucuronides with 2-hydroxycineole being the predominant metabolite at a maximum plasma concentration of 86 nmol/L followed by the 9-hydroxy isomer at a maximum plasma concentration of 33 nmol/L. The parent compound 1,8-cineole showed a low maximum plasma concentration of 19 nmol/L. In urine, 2-hydroxycineole also showed highest contents followed by its 9-isomer. Summing up the urinary excretion over 10 h, 2-hydroxycineole, the 9-isomer, the 3-isomer and the 7-isomer accounted for 20.9, 17.2, 10.6 and 3.8% of the cineole dose, respectively.
Horst
Kathie
K
Lehrstuhl für Lebensmittelchemie, Technische Universität München, Garching, Germany.
Rychlik
Michael
M
D000328:Adult; D001628:Beverages; D002247:Carbon Isotopes; D002851:Chromatography, High Pressure Liquid; D003511:Cyclohexanols / Q000097:blood / Q000378:metabolism* / Q000652:urine; D003903:Deuterium; D000077591:Eucalyptol; D005260:Female; D005421:Flavoring Agents / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D005524:Food Technology / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007201:Indicator Dilution Techniques; D007553:Isotope Labeling; D057230:Limit of Detection; D039821:Monoterpenes / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D010865:Pilot Projects; D018515:Plant Leaves / Q000737:chemistry; D027543:Salvia officinalis / Q000737:chemistry; D052617:Solid Phase Microextraction; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
C555799:2-hydroxy-1,8-cineole; D002247:Carbon Isotopes; D003511:Cyclohexanols; D005421:Flavoring Agents; D039821:Monoterpenes; D003903:Deuterium; D000077591:Eucalyptol