title: Structural elucidation of gemifloxacin mesylate degradation product.
abstract: 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.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre, RS, Brazil.|Programa de Pós-Graduação em Ciências Farmacêuticas, Curso de Farmácia, Universidade Federal do Pampa (UNIPAMPA), BR 472, Km 592, Caixa Postal 118, CEP 97508-000, Uruguaiana, RS, Brazil.
authors.forename: Clésio Soldateli
authors.initials: CS
authors.lastname: Paim
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre, RS, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Führ
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre, RS, Brazil.
authors.forename: Magda Targa
authors.initials: MT
authors.lastname: Martins
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre, RS, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Gnoatto
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Curso de Farmácia, Universidade Federal do Pampa (UNIPAMPA), BR 472, Km 592, Caixa Postal 118, CEP 97508-000, Uruguaiana, RS, Brazil.
authors.forename: Lisiane
authors.initials: L
authors.lastname: Bajerski
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre, RS, Brazil.
authors.forename: Cássia Virginia
authors.initials: CV
authors.lastname: Garcia
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre, RS, Brazil.
authors.forename: Martin
authors.initials: M
authors.lastname: Steppe
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre, RS, Brazil.
authors.forename: Elfrides Eva Scherman
authors.initials: EE
authors.lastname: Schapoval
mesh_terms: D002853:Chromatography, Liquid; D004355:Drug Stability; D024841:Fluoroquinolones / Q000032:analysis* / Q000737:chemistry*; D000077735:Gemifloxacin; D009682:Magnetic Resonance Spectroscopy; D009287:Naphthyridines / Q000032:analysis* / Q000737:chemistry*; D010782:Photolysis
chemical_list: D024841:Fluoroquinolones; D009287:Naphthyridines; D000077735:Gemifloxacin
keywords: degradation product; forced degradation; gemifloxacin mesylate; isolation and structural elucidation; stability studies