Structural elucidation of gemifloxacin mesylate degradation product

Gemifloxacin mesylate (GFM), chemically (R,S)-7-[(4Z)-3-(aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid methanesulfonate, is a synthetic broad-spectrum antibacterial agent. Although many papers have been published in the literature describing the stability of fluorquinolones, little is known about the degradation products of GFM. Forced degradation studies of GFM were performed using radiation (UV-A), acid (1 mol L(-1) HCl) and alkaline conditions (0.2 mol L(-1) NaOH). The main degradation product, formed under alkaline conditions, was isolated using semi-preparative LC and structurally elucidated by nuclear magnetic resonance (proton - (1) H; carbon - (13) C; correlate spectroscopy - COSY; heteronuclear single quantum coherence - HSQC; heteronuclear multiple-bond correlation - HMBC; spectroscopy - infrared, atomic emission and mass spectrometry techniques). The degradation product isolated was characterized as sodium 7-amino-1-pyrrolidinyl-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate, which was formed by loss of the 3-(aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl ring and formation of the sodium carboxylate. The structural characterization of the degradation product was very important to understand the degradation mechanism of the GFM under alkaline conditions. In addition, the results highlight the importance of appropriate protection against hydrolysis and UV radiation during the drug-development process, storage, handling and quality control.