Bioanalysis of six antibiotics from volumetric microsamples: a new tool for precision dosing in critically ill children

Bioanalysis. 2024 Jan;16(1):19-31. doi: 10.4155/bio-2023-0171. Epub 2023 Nov 22.

Abstract

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.

Keywords: beta-lactams; dried blood spots; glycopeptides; infectious diseases; therapeutic drug monitoring; volumetric microsampling.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Blood Specimen Collection / methods
  • Child
  • Critical Illness
  • Humans
  • Meropenem
  • Tandem Mass Spectrometry / methods
  • Vancomycin*
  • Water

Substances

  • Anti-Bacterial Agents
  • Meropenem
  • Vancomycin
  • Water