Nonvolatile compounds usually have a high molecular weight and exhibit a high boiling point, which poses great challenges to the ionization method of MS. Ambient ionization sources can efficiently analyze the nonvolatile compounds without complex pretreatment, but they generally require special media such as heating devices, laser optical devices, or corona needles. Acoustic nebulization assisted photoionization (ANPI) is a potential method for the analysis of nonvolatile compounds that uses nebulization as a prerequisite for photoionization and introduces many advantages of PI, including excellent ionization efficiency, a high yield of molecular ions, and simplified spectrum interpretation. However, the ANPI source can be limited in on-site applications by the complexity of the analytical devices and the high cost of the nebulization chip. To address this issue, in this paper, we explored cheap and commercially piezoelectric materials used in a mist sprayer and fabricated a nebulization swab assisted photoionization (NSAP) as an ambient ionization source. Some useful results are presented: numerical simulation was introduced successfully for optimizing the aerosol distribution in the NSAP source; nonvolatile muscle relaxants, drugs of abuse, antibiotics, phthalates, and cholesterol were detected mostly as their protonated molecular ions while some special acetone/water cluster ions were detected. In addition, the LOD for most of the target analytes ranged from 10.0 to 50.0 pg with RSD ≤ 9%. Finally, this method is implemented for Chinese baijiu spiked with phthalates. The experimental data shows the capability of a NSAP source in high sensitivity and on-site analysis of the nonvolatile compounds.
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