Simultaneous assay of multiple antibiotics in human plasma by LC-MS/MS: importance of optimizing formic acid concentration.
OBJECTIVE
Optimal dosing of antibiotics in critically ill patients is complicated by the development of resistant organisms requiring treatment with multiple antibiotics and alterations in systemic exposure due to diseases and extracorporeal drug removal. Developing guidelines for optimal antibiotic dosing is an important therapeutic goal requiring robust analytical methods to simultaneously measure multiple antibiotics.


METHODS
An LC-MS/MS assay using protein precipitation for cleanup followed by a 6-min gradient separation was developed to simultaneously determine five antibiotics in human plasma.


RESULTS
The precision and accuracy were within the 15% acceptance range. The formic acid concentration was an important determinant of signal intensity, peak shape and matrix effects.


CONCLUSIONS
The method was designed to be simple and successfully applied to a clinical pharmacokinetic study.
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Feng
F
Chen
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Zhe-Yi
ZY
Hu
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
S Casey
SC
Laizure
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Joanna Q
JQ
Hudson
D000900:Anti-Bacterial Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D016638:Critical Illness; D005561:Formates / Q000737:chemistry*; D006801:Humans; D057230:Limit of Detection; D053719:Tandem Mass Spectrometry
D000900:Anti-Bacterial Agents; D005561:Formates; C030544:formic acid
LC–MS/MS; cefepime; daptomycin; formic acid; matrix effects; meropenem; piperacillin/tazobactam; vancomycin