Simultaneous Assay of Multiple Antibiotics in Human Plasma by LC–MS/MS: Importance of Optimizing Formic Acid Concentration

Abstract

Aim: 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. Conclusion: The method was designed to be simple and successfully applied to a clinical pharmacokinetic study.

Keywords::

• cefepime
• daptomycin
• formic acid
• LC–MS/MS
• matrix effects
• meropenem
• piperacillin/tazobactam
• vancomycin

Financial & competing interests disclosure

This work was supported by a grant from the Oxnard Foundation of Newport Beach, CA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

We acknowledge the dialysis and ICU nurses at Methodist University Hospital in Memphis, TN and the staff at the University of Tennessee Clinical Research Center for their assistance with this study.

Additional information

Funding

This work was supported by a grant from the Oxnard Foundation of Newport Beach, CA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.