Comprehensive degradation study of lipoglycodepsipeptide antibiotic ramoplanin by liquid chromatography and mass spectrometry

•Stability indicating LC method for analysis of ramoplanin developed and validated.•Degradation products of ramoplanin elucidated by mass spectrometry.•Hydrolysis of the lacton ring is predominant path of ramoplanin's degradation.•Significant degradation of ramoplanin under alkaline conditions...

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Bibliographic Details
Published in:Talanta open 2022-08, Vol.5, p.100118, Article 100118
Main Authors: Stražić Novaković, D., Galić, N.
Format: Article
Language:English
Subjects:
Forced degradation
Liquid chromatography
Mass spectrometry
Polypeptide antibiotic
Stability indicating method
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Summary:•Stability indicating LC method for analysis of ramoplanin developed and validated.•Degradation products of ramoplanin elucidated by mass spectrometry.•Hydrolysis of the lacton ring is predominant path of ramoplanin's degradation.•Significant degradation of ramoplanin under alkaline conditions observed.•Ramoplanin degrades via asparagine deamidation under acidic conditions. 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. [Display omitted]
ISSN:2666-8319
2666-8319
DOI:10.1016/j.talo.2022.100118