Development of a Highly Efficient Decontamination Approach for Ceftolozane in the Pharmaceutical Manufacturing Environment

Publication date: Available online 29 August 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Rong-Sheng Yang, Li-Kang Zhang, Roy Helmy, Teresa Andreani, Zhijian Liu, Huaming ShengAbstractThe β-lactam core is a key structure responsible for inducing both IgE-mediated acute-onset hypersensitivity and T-cell-mediated delayed-onset hypersensitivity with penicillins in humans. There is essentially no clinically significant immunologic cross-reactivity noted between the β-lactam cores of penicillins and cephalosporins based on challenge studies in humans. The side-chains appear to be more important in inducing IgE-mediated acute-onset hypersensitivity and T-cell delayed-onset hypersensitivity with cephalosporins in humans. Despite these clinical findings, the Food and Drug Administration (FDA) still requires the level of β-lactamrelated antibiotic residues to be controlled at very low levels in a manufacturing facility. Ceftolozane is Merck & Co., Inc., Kenilworth, NJ, USA’s (MSD’s) 5th generation broad-spectrum cephalosporin antibiotic against gram-negative bacteria. During the initial effort in searching for the decontamination method of ceftolozane, it was found that common degradation methods were very slow in opening the β-lactam ring in ceftolozane. Moreover, most of the previously reported decontamination methods applied analytical methods that only monitored the disappearance of the parent molecule as the endpoint of degradation. In this way,...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research