Quantification of Cefepime, Meropenem, Piperacillin and Tazobactam in Human Plasma using a Sensitive and Robust LC-MS/MS Method- Part II. Stability Evaluation [PublishAheadOfPrint]

Although the stability of β-lactam antibiotics is a known issue, none of the previously reported bioanalytical methods had an adequate evaluation on their stability. In the current study, the stability of cefepime, meropenem, piperacillin, and tazobactam under various conditions was comprehensively evaluated. The evaluated parameters include stock solution stability, short-term stability, long-term stability, freeze-thaw stability, processed sample stability and whole blood stability. When stored at -20 °C, the stock solution of meropenem in methanol is stable for up to 3 weeks, and the stock solutions of cefepime, piperacillin, and tazobactam are stable for up to 6 weeks. All four antibiotics were stable in human plasma for up to 3 months when stored at -80 °C and stable in whole blood for up to 4 hours at room temperature. Short-term stability results indicated that all four β-lactams are stable at room temperature for 2 hours, but substantial degradation was observed when their plasma samples were stored at room temperature for 24 hours, with the degradation of cefepime, meropenem, piperacillin and tazobactam being 30.1 %, 75.6 %, 49.0 % and 37.7 %, respectively. As the stability information is method-independent, our stability results can be used as a reference by other research groups that work with these antibiotics.

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