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 (dClO), 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 dClO 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/cm of each cephalosporin and exposed to 9600 ppm-h of dClO, followed by UPLC-MS/MS analysis (phase 1). Cephalosporins underwent degradation assessment after exposure to ClO in an aqueous solution (phase 2). In total, 100μg of each compound was subjected to 400 ppm of dClO 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 cultures to evaluate the biological activities of the degradants.

RESULTS

The 9600 ppm-h of ClO exposure effectively degraded all cephalosporin compounds to levels <0.002 μg/cm 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 dClO, combined with UPLC-MS/MS and biological activity testing, has significant potential to enable facility repurposing for the production of non-beta-lactam compounds.