Synthesis and application of quaternary amine-functionalized core-shell-shell magnetic polymers for determination of metabolites of benzene, toluene and xylene in human urine samples and study of exposure assessment.

ABSTRACT

As production processes have evolved, airborne concentrations of benzene, toluene and xylene in many workplaces are already well below the occupational exposure limits. However, studies have shown that low levels of exposure to benzene, toluene and xylene can still cause health effects in people exposed occupationally. However, there is no literature on health risk assessment of internal exposure. In view of this, an analytical method based on quaternary amine-functionalized core-shell-shell magnetic polymers (QA-CSS-MPs) was developed for the determination of seven metabolites in urine by MSPE-UPLC-DAD-HRMS. Furthermore, an improved QuEChERS method for the extraction of seven metabolites from human urine samples was introduced for the first time and satisfactory extraction rates were achieved. In addition, QA-CSS-MPs microspheres with core-shell-shell structure were designed and synthesized, and the morphology, composition and magnetic properties of the materials were fully characterized to verify the rationality of the synthetic route. Subsequently, QA-CSS-MPs microspheres were used as magnetic solid-phase extraction (MSPE) adsorbents for the purification of urine extracts, and UPLC-DAD-HRMS was used for the detection of seven metabolites. As a result, this method allows the accurate determination of seven metabolites in urine samples over an ultra-wide concentration range (0.001-100 mg/L). Under optimal experimental conditions, i.e., 2% hydrochloric acid in urine for the hydrolysis and 20 mg of QA-CSS-MPs for 5 min purification, the spiked recoveries of the seven target metabolites ranged from 81.5% to 117.7% with RSDs of 1.0%-9.4%. The limits of detection (LODs, S/N≥3) for the established method were in the range of 0.2-0.3 µg/L. The developed method was applied to 254 human urine samples for the determination of seven metabolites. The results showed that the concentration distributions of three xylene metabolites in urine, 2-MHA, 3-MHA, 4-MHA and total MHA, showed statistically significant differences for occupational exposure (p<0.001). In addition, the results of the internal exposure assessment showed that there is a high potential health risk associated with occupational exposure processes.