Stability of clavulanic acid in PEG/citrate and liquid–liquid extraction in aqueous two-phase system

• Autor(a) principal: Carneiro-da-Cunha, M. N.
• Data de Publicação: 2014
• Outros Autores: Souza, K. P. S., Mota, A., Teixeira, J. A., Porto, C. S., Porto, Tatiana Souza, Porto, Ana L. F.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/31469
• topic: Clavulanic acid; ATPS; PEG; Citrate salts; Stability; Science & Technology

β-Lactamases are enzymes responsible for the hydrolysis of β-lactam antibiotics, being produced by several pathogenic bacteria. Clavulanic acid is a commercially and clinically important β-lactamase inhibitor, its extraction being possible by the application of aqueous two-phase system. In this study, clavulanic acid stability was investigated at different molar mass PEG (400, 1 000 and 20 000 g mol−1) and at different citrate concentrations (5 and 20%) PEG/citrate aqueous-two phase systems (ATPS), under different pH values (4.0–8.0). Clavulanic acid extraction was also evaluated. Low citrate concentration and PEG 20 000 (g mol−1) ATPS, at pH 6.0, were shown to be the systems that presented the highest clavulanic acid stability. Based on this, a factorial design 22 was used to evaluate CA extraction, being PEG (20, 25 and 30%) and citrate (5, 10 and 15%) concentrations the parameters evaluated. Clavulanic acid was extracted into the PEG-rich phase (133.66 mg L−1), the highest values of the partition coefficient and yield being K = 5.92, Y = 103.53%, respectively The ATPS was not only effective on clavulanic acid extraction, but also its degradation was minimal. These results clearly indicate that ATPS can be successfully applied as a first step for the purification of clavulanic acid.