Catalytic behavior of nitrous acid for acetaminophen transformation during the freezing process

This study demonstrates the transformation of acetaminophen by reactive nitrous acid in a frozen solution and its abnormal stoichiometry. The chemical reaction between acetaminophen and nitrous acid (AAP/NO₂^- system) was negligible in the aqueous solution; however, the reaction rapidly progressed if the solution started to freeze. The ultrahigh performance liquid chromatography-electrospray ionization tandem mass spectrometry measurements showed that polymerized acetaminophen and nitrated acetaminophen were formed in the proceeding reaction. Electron paramagnetic resonance spectroscopy measurements showed that nitrous acid oxidized acetaminophen via a one-electron transfer reaction producing acetaminophen-derived radical species, which is the cause of acetaminophen polymerization. We demonstrated that a relatively smaller dose of nitrite than acetaminophen caused significant acetaminophen degradation in the frozen AAP/NO₂^- system and revealed that the dissolved oxygen content notably affected acetaminophen degradation. We showed that the reaction occurs in a natural Arctic lake matrix (nitrite and acetaminophen spiked). Considering that the freezing phenomenon is common in the natural environment, our research provides a possible scenario for the freezing chemistry of nitrite and pharmaceuticals in environmental chemistry.