Ethyl chloroformate mediated gas chromatographic-mass spectrometric biomonitoring of acidic biomarkers of occupational exposure and endogenous metabolites in human urine.

Numerous industrial organic pollutants such as aromates, alkoxyalcohols, other organic solvents and monomers are absorbed, metabolized, and finally excreted in urine mostly as carboxylic acids that are determined as biomarkers of exposure. For a number of these xenometabolites, biological limits (levels of biomarkers in biological material) have been established to prevent damage to human health. Till now, most of the analytical procedures used have been optimized for one or a few analytes. Here, we report a more comprehensive approach enabling rapid GC-MS screening of sixteen acidic biomarkers in urine that are metabolized in the human body from several important industrial chemicals; benzene, toluene, styrene, xylenes, alkoxyalcohols, carbon disulfide, furfural and N,N-dimethylformamide. The new method involves immediate in situ derivatization - liquid liquid microextraction of urine by an ethyl chloroformate-ethanol-chloroform-pyridine medium and GC-MS analysis of the derivatized analytes in the lower organic phase. The xenometabolite set represents diverse chemical structures and some of hippuric and mercapturic acids also provided unusual derivatives that were unambiguously elucidated by means of new ethyl chloroformates labeled with stable isotopes and by synthesis of the missing reference standards. In the next step, an automated routine was developed for GC-MS/MS analysis using a MetaboAuto® sample preparation workstation and the new method was validated for fourteen metabolites over the relevant concentration range of each analyte in the spiked pooled human urine. It shows good linearity (R

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Declaration of Competing Interest The authors have no conflict of interest to declare.