Chlorine Dioxide Dry Gas: A Promising Solution for Effective Decontamination of Cephalosporin Compounds

Introduction: Cephalosporins can trigger hypersensitivity reactions in certain individuals. Consequently, strict regulations restrict the production of non-beta-lactam substances during or after cephalosporin manufacturing. Dry chlorine dioxide gas (dClO₂), together with ultra-performance liquid chromatography Mass spectrometry/mass spectrometry (UPLC-MS/MS) detection methods, has emerged as a promising method for decontaminating cephalosporin compounds. This study aimed to assess whether a standardized dClO₂ and testing protocol could provide successful decontamination of a broad spectrum of cephalosporins while also providing an indicative assessment of degradants and their biological activity.

Methods: Chemical indicators (CIs) mimicking different surfaces (stainless steel, Perspex^®, aluminum) were contaminated with 1 μg/cm² of each cephalosporin and exposed to 9600 ppm-h of dClO₂, followed by UPLC-MS/MS analysis (phase 1). Cephalosporins underwent degradation assessment after exposure to ClO₂ in an aqueous solution (phase 2). In total, 100μg of each compound was subjected to 400 ppm of dClO₂ for 24 h (9600 ppm-h), followed by UPLC-MS/MS analysis. Antimicrobial susceptibility disks (30 μg) of cefaclor underwent identical treatment cycles and UPLC-MS/MS analysis. Subsequently, these disks were placed in Escherichia coli cultures to evaluate the biological activities of the degradants.

Results: The 9600 ppm-h of ClO₂ exposure effectively degraded all cephalosporin compounds to levels <0.002 μg/cm² on surfaces (phase 1), <2 ppb in solution, and <0.02 μg/disk (phase 2). The antimicrobial efficacy of cefaclor was nullified after the same exposure, confirming complete inactivation of the degradants.

Conclusion: A decontamination protocol utilizing dClO₂, combined with UPLC-MS/MS and biological activity testing, has significant potential to enable facility repurposing for the production of non-beta-lactam compounds.