Talanta Open (Aug 2022)
Comprehensive degradation study of lipoglycodepsipeptide antibiotic ramoplanin by liquid chromatography and mass spectrometry
Abstract
Development of new antibiotics is of the utmost importance in the battle against antimicrobial resistance. One of the promising candidates in the fight against resistant bacteria is ramoplanin, a cyclic lipoglycodepsipeptide derived from a fermentation broth. In order to obtain effective and safe pharmaceutical product on the market, development of reliable analytical method for the evaluation of ramoplanin's purity is vital. In the present work, an LC method was developed, validated and used during stability testing of ramoplanin, in solid state and in solution. Forced degradation study was performed by subjecting the sample to different stress conditions (acid and base hydrolysis, oxidation, humidity, heat and light) and the observed degradation products were elucidated using mass spectrometry. The study revealed significant degradation of ramoplanin under alkaline conditions, leading to formation of lacton hydrolysis product. The results of the study clearly demonstrate that the hydrolysis of the lacton ring is predominant path of ramoplanin's degradation. However, other significant degradation routs were also observed. Based on the MS/MS results, degradation pathways of ramoplanin are proposed.
