title: Quantification of four major metabolites of embryotoxic N-methyl- and N-ethyl-2-pyrrolidone in human urine by cooled-injection gas chromatography and isotope dilution mass spectrometry.
abstract: N-Methyl- and N-ethyl-2-pyrollidone (NMP and NEP) are frequently used industrial solvents and were shown to be embryotoxic in animal experiments. We developed a sensitive, specific, and robust analytical method based on cooled-injection (CIS) gas chromatography and isotope dilution mass spectrometry to analyze 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), two newly identified presumed metabolites of NEP, and their corresponding methyl counterparts (5-HNMP, 2-HMSI) in human urine. The urine was spiked with deuterium-labeled analogues of these metabolites. The analytes were separated from urinary matrix by solid-phase extraction and silylated prior to quantification. Validation of this method was carried out by using both, spiked pooled urine samples and urine samples from 56 individuals of the general population with no known occupational exposure to NMP and NEP. Interday and intraday imprecision was better than 8% for all metabolites, while the limits of detection were between 5 and 20 μg/L depending on the analyte. The high sensitivity of the method enables us to quantify NMP and NEP metabolites at current environmental exposures by human biomonitoring.
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Ruhr-University Bochum (IPA), Bochum, Germany. schindler@ipa-dguv.de
authors.forename: Birgit K
authors.initials: BK
authors.lastname: Schindler
authors.forename: Stephan
authors.initials: S
authors.lastname: Koslitz
authors.forename: Swetlana
authors.initials: S
authors.lastname: Meier
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Belov
authors.forename: Holger M
authors.initials: HM
authors.lastname: Koch
authors.forename: Tobias
authors.initials: T
authors.lastname: Weiss
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Heiko U
authors.initials: HU
authors.lastname: Käfferlein
mesh_terms: D000293:Adolescent; D000328:Adult; D002849:Chromatography, Gas; D005260:Female; D015386:Hazardous Substances / Q000652:urine; D006801:Humans; D057230:Limit of Detection; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011760:Pyrrolidinones / Q000737:chemistry* / Q000652:urine*; D011865:Radioisotope Dilution Technique; D013388:Succinimides / Q000737:chemistry / Q000652:urine; D055815:Young Adult
chemical_list: C107901:2-hydroxy-N-methylsuccinimide; D015386:Hazardous Substances; C523727:N-ethyl-2-pyrrolidone; D011760:Pyrrolidinones; D013388:Succinimides