Determination of worst-case cephalosporin residues in laboratory glassware using a validated low-level RP-HPLC method

Abstract

Cephalosporin antibiotics are highly allergenic and present serious cross contamination problems in analytical and manufacturing environments. Regulatory agencies require quality control laboratories to establish strict zero-tolerance or health-based carryover exposure limits, making verification of equipment and glassware cleanliness extremely important. The aim of this study was to assess the efficiency of cleaning laboratory glassware procedures by identifying the level of residual contamination of a worst-case cephalosporin antibiotic, cefixime. A validated reverse-phase liquid chromatographic technique was used to measure chemical residues of cefixime, with the remaining detergent contamination measured by conductivity of final rinse water. Cefixime and its related impurities were separated on a C18 reverse-phase column using an environmentally friendly isocratic mobile phase of acetate buffer with a pH of 6.5 and ethanol in an 89:11 (v/v) ratio, and UV was used to detect cefixime at 254 nm. The technique was sensitive, selective, and linear at low levels appropriate in the analysis of residues on glass surfaces. Recovery experiments verified the capability of the approach to find cefixime residues that were left behind after normal cleaning activities. Conductivity measurements were used to demonstrate the effective removal of detergent residue, that could not be adequately detected at 254 nm. The integrated analytical method provides a scientifically grounded and regulatory-applicable approach to holistic cleaning validation of laboratory glassware, which facilitates the control of contamination in pharmaceutical analytical facilities without violating the postulates of green analytical chemistry.