Bioanalysis of six antibiotics from volumetric microsamples: a new tool for precision dosing in critically ill children.
John Takyi-WilliamsAbbie D LeinoRuiting LiKevin James DownesAthena F ZuppaAmanda BwintBo WenDuxin SunMarc H ScheetzManjunath Amit P PaiPublished in: Bioanalysis (2023)
Background: Volumetric absorptive microsamples (VAMS) can support pharmacokinetic / pharmacodynamic studies. We present the bioanalytical method development for the simultaneous quantification of ampicillin, cefepime, ceftriaxone, meropenem, piperacillin, tazobactam, and vancomycin from VAMS. Methods & results: Optimal extraction, chromatographic, and mass spectrometry conditions were identified. Maximum extraction recoveries included 100 μl of water for rehydration and methanol for protein precipitation. Chromatographic separation used Phenomenex Kinetex ™ Polar C18 column with a mobile phase comprising water/acetonitrile with formic acid and was fully validated. Hematocrit effects were only observed for vancomycin. Samples were stable for 90 days at -80°C except for meropenem, which was stable for 60 days. Conclusion: Multiple antibiotics can be assayed from a single VAMS sample to facilitate pharmacokinetic/pharmacodynamic studies.
Keyphrases
- liquid chromatography
- mass spectrometry
- simultaneous determination
- gram negative
- methicillin resistant staphylococcus aureus
- case control
- tandem mass spectrometry
- young adults
- high performance liquid chromatography
- multidrug resistant
- high resolution
- solid phase extraction
- binding protein
- ionic liquid
- small molecule
- carbon dioxide