title: Determination of metabolites of di(2-ethylhexyl) terephthalate (DEHTP) in human urine by HPLC-MS/MS with on-line clean-up.
abstract: Di(2-ethylhexyl) terephthalate (DEHTP) is used as a substitute for ortho-phthalate based plasticizers like di(2-ethylhexyl) phthalate (DEHP) which are discussed and regulated due to their reproductive toxicity. We developed a fast and rugged method to quantify side chain oxidized monoesters of DEHTP in human urine, namely 5OH-MEHTP, 5oxo-MEHTP, 2cx-MMHTP and 5cx-MEPTP. Sample preparation was kept simple with enzymatic deconjugation and a two column assembly for on-line sample clean up. Metabolites were identified with authentic standards and quantified via isotope dilution LC-MS/MS. The limit of quantification was 0.2μg/L for 5cx-MEPTP and 5oxo-MEHTP, 0.3μg/L for 5OH-MEHTP and 0.4μg/L for 2cx-MMHTP. Accuracy (relative recovery: 95.8-111%) and precision (relative standard deviation: <7%) were highly acceptable. In a pilot biomonitoring study with 34 volunteers (aged 25-61 (median 42), 20 female and 14 male) not known to be occupationally exposed to DEHTP, we could detect 5cx-MEPTP above the limit of quantification in 94% of the samples (median: 0.9μg/L, maximum: 38.7μg/L). The other metabolites investigated were detected at a lower rate and at lower concentration levels (5oxo-MEHTP: 21%, maximum: 1.8μg/L; 5OH-MEHTP: 18%, maximum: 3.4μg/L; 2cx-MMHTP: 9%, maximum: 0.9μg/L). All target analytes can be regarded as promising and specific urinary biomarkers for DEHTP exposure. With this method we provide a basis for quantitatively investigating the human metabolism of DEHTP and for performing exposure and risk assessments in the general population and the working environment.
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Lessmann
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Schütze
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weiss
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. Electronic address: koch@ipa-dguv.de.
authors.forename: Holger M
authors.initials: HM
authors.lastname: Koch
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010795:Phthalic Acids / Q000378:metabolism / Q000652:urine*; D010968:Plasticizers / Q000032:analysis* / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010795:Phthalic Acids; D010968:Plasticizers; C053316:di-(2-ethylhexyl) terephthalate
keywords: DEHTP; Di(2-ethylhexyl) terephthalate; Exposure assessment; Human biomonitoring; Plasticizer; Urinary metabolite