In general, the determined values were in good agreement with the reference values of both SRMs especially given the extensive scope of the new workflow with recoveries ranging from 74% to 124% in SRM1950 and recoveries between 81% and 115% in SRM3672 (Figure ). These recoveries are similar to values reported in the literature for SRM3672 by (80.5% -105%) and . In the reference materials, several additional metabolites and xenobiotics were quantified (Figure , Table ). In SRM3672, 18 xenobiotics and two estrogens were detected. SRM1950 was contaminated with 17 xenobiotics, with nine of them being detected in both reference materials, including personal care product ingredients (methylparaben, propylparaben, phydroxybenzoic acid, benzophenone-1), phytoestrogens (genistein, daidzein), smoking markers (cotinine, trans-3-OH-cotinine) and an industrial side product (2-naphthol). In SRM3672, additional phytoestrogens (e.g. enterolactone, enterodiol, daidzein, glycitein), a plasticizer (mono butyl phthalate) and butylparaben were observed, whereas, in SRM1950, scopolamine, a phytotoxin, perfluorinated substances (PFOA, PFOS), industrial side products (nonylphenol, 4-tert-octylphenol) and other plasticizers (BPS, BPA) were found. The quantified metabolome comprised 48 (SRM1950) and 61 (SRM3672) additional compounds, respectively. Smoker's urine was not enzyme-treated for the evaluation. Mainly amino acids, nucleobases and nucleosides were quantified in these samples. The concentrations ranged over four orders of magnitude for metabolites in the urine plasma reference material. This range spanned even over six orders of magnitude when expanding to exogenic contaminants. In the urine reference material, concentrations were less variable covering three orders of magnitude.