Quantification of 1,8-cineole and of its metabolites in humans using stable isotope dilution assays

Authors

  • Kathie Horst,

    1. Lehrstuhl für Lebensmittelchemie, Technische Universität München, Garching, Germany
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  • Michael Rychlik

    Corresponding author
    1. Lehrstuhl für Lebensmittelchemie, Technische Universität München, Garching, Germany
    • Chair of Analytical Food Chemistry, Technische Universität München, Alte Akademie 10, D-85350 Freising, Germany Fax: +49-8161714216
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    • Current address: Professor Michael Rychlik, BIOANALYTIK Weihenstephan, Z I E L Research Center for Nutrition and Food Sciences, Technische Universität München, Alte Akademie 10, D-85350 Freising, Germany


Abstract

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 [2H3]-1,8-cineole, [9/10-2H3]-2-hydroxy-1,8-cineole and [13C,2H2]-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.

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