Aqueous ozonation of the antiviral drug umifenovir (Arbidol): Reaction pathways and transformation products.

The advancement of ozonation for wastewater treatment requires a thorough understanding of transformation processes affecting emerging contaminants such as pharmaceuticals and personal care products (PPCPs). This study investigates the degradation products of umifenovir (Arbidol) during aqueous ozonation. Using HPLC-ESI-HRMS, 23 primary (intermediate) transformation products were identified, their structures proposed, and degradation pathways established. The highest product diversity occurred at neutral pH due to reactions involving both molecular ozone and hydroxyl radicals. Initial transformation pathways include sulfide group oxidation with thiophenol moiety elimination, and indole ring oxidation followed by debromination. Under excess ozonation, GC-HRMS and mixed-mode (WAX/WCX) HPLC-HRMS revealed over 42 low-molecular-weight deep degradation products. Most arise from parent molecule transformation (e.g., trimethylamine or thiophenol) and subsequent oxidation. In addition to expected products, side radical reactions such as chlorination and dealkylation were observed. The bromine atom in umifenovir enabled HPLC-ICP-MS quantification of bromine-containing transformation products without individual standards. Umifenovir is rapidly removed from the reaction medium; however, persistent intermediate and deep transformation products remain even under excess ozonation. These findings highlight the need for advanced analytical methods for transformation product identification and for evaluating ozonation efficiency based on product formation rather than parent compound removal alone.