Tancock-Jones Rhys, Cole Brett, Martens Jeremy, Heckenberg Allan, Rattenbury Simon
Royal Society of Biology, London, United Kingdom.
Association for Biosafety for Australia and New Zealand (ABSANZ), Victoria, Australia.
Appl Biosaf. 2024 Dec 16;29(4):232-240. doi: 10.1089/apb.2023.0023. eCollection 2024 Dec.
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.
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.
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.
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.
头孢菌素可在某些个体中引发过敏反应。因此，严格的规定限制了头孢菌素生产过程中或之后非β-内酰胺物质的产生。干燥二氧化氯气体（dClO）与超高效液相色谱质谱/质谱（UPLC-MS/MS）检测方法一起，已成为一种有前景的头孢菌素化合物去污方法。本研究旨在评估标准化的dClO和测试方案是否能成功地对多种头孢菌素进行去污，同时还能对降解产物及其生物活性进行指示性评估。
模拟不同表面（不锈钢、有机玻璃、铝）的化学指示剂（CIs）被每种头孢菌素以1μg/cm的量污染，并暴露于9600 ppm-h的dClO中，随后进行UPLC-MS/MS分析（阶段1）。头孢菌素在水溶液中暴露于ClO后进行降解评估（阶段2）。每种化合物总共100μg，暴露于400 ppm的dClO中24小时（9600 ppm-h），随后进行UPLC-MS/MS分析。头孢克洛的抗菌药敏纸片（30μg）经过相同的处理周期和UPLC-MS/MS分析。随后，将这些纸片置于培养物中以评估降解产物的生物活性。
9600 ppm-h的ClO暴露有效地将所有头孢菌素化合物在表面降解至<0.002μg/cm（阶段1），在溶液中<2 ppb，在纸片中<0.02μg/片（阶段2）。相同暴露后头孢克洛的抗菌效力丧失，证实降解产物完全失活。
利用dClO的去污方案，结合UPLC-MS/MS和生物活性测试，具有使设施重新用于生产非β-内酰胺化合物的巨大潜力。
