Publication:

Rapid Determination of Clavulanic Acid in Submerged Cultures of Streptomyces clavuligerus as an Alternative Method for Bioprocess Monitoring and Control

Resumen en inglés

Clavulanic acid (CA) is a β-lactamase inhibitor widely used in combination with β-lactam antibiotics to overcome bacterial resistance, and it is produced by Streptomyces clavuligerus through submerged fermentation. To ensure its industrial-scale production, it is essential to develop analytical methods that are rapid, reliable, and suitable for process monitoring. In this work, a UV–VIS spectrophotometric method was developed and validated for the quantification of CA in simulated fermentation matrices, employing ethyl acetate as the solvent for liquid–liquid extraction. The method demonstrated linearity in the range of 100–600 ppm (R² > 0.98), with coefficients of variation below 3% and recovery rates ranging from 90% to 110%. Clavulanic acid remained stable for up to 72 h under refrigeration, and complete transfer to the organic phase was achieved within 40 min. No significant interferences were detected, and the method showed adequate sensitivity (LOD: 60 ppm; LOQ: 100 ppm). These results confirm that the proposed method is a fast, cost-effective, and reproducible alternative to chromatographic techniques such as HPLC, representing a practical tool for routine bioprocess monitoring and quality control in the industrial production of clavulanic acid.