Extraction of Cephalosporin Antibiotics with Aqueous Two-phase Systems Composed of Water-miscible Organic Solvents and Salts

The beta-lactam antibiotics such as penicillin and cephalosporin account for over 65% of the market. Development of a more effective separation technique is desired to extract and purify the biologically active cephalosporin antibiotics. In this study, to recover cephalosporin antibiotics, cephalosporin C and cephalexin, an aqueous two-phase system (ATPS) composed of a water-miscible organic solvent and salts was used. For cephalosporin C extraction with the ATPS, the extent of extraction of cephalosporin C was small because of its high hydrophilicity. For cephalexin, which is more hydrophobic, it was successfully extracted with ATPS. From binodal experiments, tetrahydrofuran (THF), 1-propanol and acetone were selected as the candidates for the extraction solvent. In the extraction experiments, THF was found to be suitable because it gave the highest extractability of cephalexin and the lowest water content in the top (solvent) phase among the candidates. When the initial volume ratio of water to solvent was unity, the maximum distribution ratio was 3.13. The value of the distribution ratio increased up to 9.87 with increasing initial volume ratio. The ATPS composed of a water-miscible organic solvent and salt was found to be promising for purification of antibiotics under such mild conditions.