Monitoring the Formation of Oxygen-Rich Functional Groups by ¹⁸ O Ozonation of Pharmaceuticals Containing S- and N-Scaffolds

The removal of compounds of emerging concern (CECs) from wastewater is essential due to their potential environmental and health impacts. Ozonation has been shown to reduce CEC concentrations; however, concerns remain about the formation of potentially hazardous ozonation products (OPs). This study focuses on assessing the formation of OPs from sulfur and nitrogen compounds in wastewater treatment by using 18O-enriched ozonation and mass spectrometry (MS). Compounds were selected based on their ozone-reactive functional groups, and 18O-labeled ozone was used to track the formation of the resulting ozonation products of oxygen transfer reactions. The 18O/16O ratio of the OPs showed that sulfoxides were formed from thioethers (penicillin G) by direct oxygen transfer and sulfonic acids from thiols (cysteine) through consecutive ozone attacks with oxygen transfer reactions being the main formation pathway. Similarly, nitro group formation from primary amines (sitagliptin) occurs through two consecutive ozone attacks. In contrast, for secondary amines (metoprolol) the nitro group was not detected, instead hydroxylated compounds were observed. The screening for specific neutral losses and product ions resulted in the detection of 11 previously unknown sulfonated OPs from two thiol-containing compounds (tiopronin and captopril). These findings advance the understanding of ozonation behavior and enhance OP detection compared to other approaches in environmental water samples.