Quantification of Cefepime, Meropenem, Piperacillin, and Tazobactam in Human Plasma Using a Sensitive and Robust Liquid Chromatography-Tandem Mass Spectrometry Method, Part 2: Stability Evaluation

Antimicrob Agents Chemother. 2018 Aug 27;62(9):e00861-18. doi: 10.1128/AAC.00861-18. Print 2018 Sep.


Although the stability of β-lactam antibiotics is a known issue, none of the previously reported bioanalytical methods had an adequate evaluation of the stability of these drugs. In the current study, the stability of cefepime, meropenem, piperacillin, and tazobactam under various conditions was comprehensively evaluated. The evaluated parameters included 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 was stable for up to 3 weeks, and the stock solutions of cefepime, piperacillin, and tazobactam were 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 were stable in whole blood for up to 4 h at room temperature. Short-term stability results indicated that all four β-lactams were stable at room temperature for 2 h, but substantial degradation was observed when the plasma samples were stored at room temperature for 24 h, with the degradation rates for cefepime, meropenem, piperacillin, and tazobactam being 30.1%, 75.6%, 49.0%, and 37.7%, respectively. Because the stability information is method independent, our stability results can be used as a reference by other research groups that work with these antibiotics.

Keywords: LC-MS/MS; human plasma; stability; validation; β-lactams.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Cefepime / metabolism*
  • Chromatography, Liquid
  • Drug Stability
  • Humans
  • Meropenem / metabolism*
  • Piperacillin / metabolism*
  • Tandem Mass Spectrometry
  • Tazobactam / metabolism*
  • Temperature


  • Anti-Bacterial Agents
  • Cefepime
  • Meropenem
  • Tazobactam
  • Piperacillin