title: Identification of thymol phase I metabolites in human urine by headspace sorptive extraction combined with thermal desorption and gas chromatography mass spectrometry.
abstract: Development of a novel highly sensitive headspace sorptive extraction (HSSE) method in combination with thermal desorption gas chromatography coupled to a mass spectrometer (TD-GC/MS) allowed the identification of thymol and several phase I metabolites in human urine. Combined with an enzymatic hydrolysis of glucuronated or sulphated phase II metabolites of thymol and of the respective phase I metabolites prior to analysis, even trace quantities of hitherto not detected thymol phase I metabolites could be identified in urine samples of test persons after oral administration of 50mg thymol. It was proven, that human metabolism leads to a hydroxylation of the aromatic ring as well as of the iso-propyl side chain. Hydroxylation of the iso-propyl group results in the formation of the rather unstable p-cymene-3,8-diol and the corresponding dehydration product p-cymene-3-ol-8-ene which could be clearly detected in human urine samples. Furthermore, the aromatic hydroxylation products p-cymene-2,5-diol, its oxidation product p-cymene-2,5-dione and p-cymene-2,3-diol were also unambiguously identified by comparison with synthesized reference compounds.
authors.affiliation: Institute of Analytical Chemistry, Johannes-Kepler-University, Altenbergerstrasse 69, A-4040 Linz, Austria. bernhard.thalhamer@jku.at
authors.forename: Bernhard
authors.initials: B
authors.lastname: Thalhamer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Buchberger
authors.forename: Mario
authors.initials: M
authors.lastname: Waser
mesh_terms: D000328:Adult; D005591:Chemical Fractionation / Q000379:methods; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D050216:Metabolic Detoxication, Phase I; D013943:Thymol / Q000378:metabolism* / Q000652:urine*
chemical_list: D013943:Thymol