Abstract

Phthalate diesters are toxic compounds found in personal care products and soaps that consist of a benzene ring with two ortho-substituted ester substituents. Phthalates are excreted after glucuronidation. However other possible metabolic pathways have not been examined. One possible route, amino acid conjugation, has been observed in compounds that are structurally similar to phthalate monoesters. An amino acid conjugate of monoethyl phthalate (MEP) was synthesized in the lab with a relatively low yield (<10%). LC/MS, LC/MS/MS, IR, and NMR instrumentation were all utilized in the analysis of the synthesis product. A product ion scan was performed on the compound using 252 and 209 m/z as precursor ions in positive ion mode. LC peaks and corresponding mass spectrum data collected for the compound demonstrated a fragmentation pattern comparable to MEP, with abundant masses of 149 and 177 m/z. The product was used as a standard for the analysis of human urine using the same instrumentation methods. A series of full scans and SIM scans were completed for urine extracts to identify candidate chromatogram peaks for subsequent product ion scans to elucidate the presence or absence of the desired compound. A pepsin digestion was performed on both the standard and one of the urine samples to attempt to identify amino acids present within the analytes of interest. Digestion of both the synthesis product and extract resulted in near or total disappearance of chromatogram peaks from precursor ions of the proposed conjugates, which was most likely a result of pepsin cleavage. The synthesis and characterization coupled with pepsin digestion of the samples provided evidence that suggests amino acid conjugation may be a feasible route of metabolism for phthalate monoesters. Proving phthalate monoesters follow this metabolic pathway would have lasting ramifications by increasing exposure estimates stemming from previously unknown metabolites.

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