Effects of biobanking conditions on six antibiotic substances in human serum assessed by a novel evaluation protocol.

BACKGROUND: Although therapeutic drug monitoring (TDM) for antibiotics in critically ill patients is recommended by expert panels, no commercial tests are available for most antibiotics. Therefore, we previously developed a multi-analyte method for the quantification of piperacillin, tazobactam, cefepime, meropenem, ciprofloxacin and linezolid in serum. However, limited stability data were available, and the relevant studies did not address the coefficients of variation of the methods applied, which may be important for verifying the storage dependency of the observed effects. Here we aimed to evaluate the storage effects of antibiotics by applying a novel evaluation protocol.
METHODS: Serum-based test samples were aliquoted and stored at room temperature, 4 °C, -20 °C or -80 °C for up to 180 days. Using an innovative evaluation protocol (considering the coefficient of variation, p-value, and criterion of monotony of observed changes), we assessed whether relevant changes (defined as ≥15% in comparison with baseline) were storage dependent (defined as substantial changes).
RESULTS: Storage at -80 °C for up to 180 days did not lead to substantial changes for any analyte. In contrast, storage at -20 °C induced substantial decreases after ≥7 days for piperacillin, tazobactam, cefepime and meropenem; after 90 days at -20 °C, only ≤23% of the initial concentrations were found for these parameters. No substantial changes were observed for linezolid and ciprofloxacin at any storage condition. All of the observed substantial changes were monotonic decreases.
CONCLUSIONS: We recommend a storage temperature of -80 °C for β-lactam antibiotics. The applied evaluation protocol yielded conclusive results and may be generally useful for stability studies.