Study of Degradation Kinetics and Structural Analysis of Related Substances of Ceftobiprole by HPLC with UV and MS/MS Detection

Abstract

Ceftobiprole is a novel β-lactam antibiotic, active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus and penicillin-resistant Streptococcus pneumoniae. To artificially generate potential degradation products (DPs) of ceftobiprole that may be formed under relevant storage conditions, acidic, alkaline, oxidative, photolytic and thermolytic stress tests were performed in both solution and solid state. A novel selective HPLC method was developed for the separation of ceftobiprole from its DPs and synthesis by-products (SBPs) using Kinetex Biphenyl column, ammonium acetate buffer pH 5.8 and acetonitrile. The kinetic studies demonstrated the low stability of ceftobiprole in alkaline solution, in the presence of an oxidising agent and under irradiation with near UV. In the solid state, ceftobiprole underwent oxidation when the powder was irradiated with visible light and UV. Based on mass spectroscopic analysis, 13 new structural formulas of SBPs and DPs were proposed, along with molecular formulas for three other DPs obtained in solution and four oxidative DPs characteristic of solid-state degradation.