Structural Elucidation of a Dimeric Impurity in the Process Development of Ceftolozane using LC/HRMS and 2D-NMR

Publication date: Available online 26 May 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Jing Liao, Huaming Sheng, Josep Saurí, Rong Xiang, Gary MartinAbstractCeftolozane is MSD’s 5th generation cephalosporin antibiotic with broad-spectrum gram-negative activity. While refining the synthetic route to the drug substance, a dimeric impurity was observed in the final active pharmaceutical ingredient (API) of ceftolozane. Through impurity enrichment and preparative isolation, the structure of the impurity was subsequently established through LC/HRMS, HRMSMS, H/D exchange and 2D-NMR studies. A kinetic study of the impurity formation was conducted to determine the best conditions to control it in the final chemical process.
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research