Development of an HPLC–MS/MS Method for the Determination of Ceftolozane/Tazobactam in Bronchoalveolar Lavage Fluid

Abstract

Aim: We describe the validation of an HPLC–MS/MS method to analyze ceftolozane and tazobactam simultaneously in saline matrixes. Materials & methods: An Agilent 1260 HPLC interfaced to an Agilent 6470 triple-quadrupole mass spectrometer was used for quantification. A reverse-phase column running a gradient of water and acetonitrile containing 0.1% formic acid mobile phase at a flow rate of 1.0 ml/min provided chromatographic fractionation. Tazobactam¹⁵N₃ was used as the internal standard. The standard curves were linear over a range of 0.02–0.5 μg/ml. Conclusion: This methodology represents a simple, reproducible approach to the determination of drug concentrations with accuracy and precision for pharmacokinetic studies undertaken with this recently US FDA-approved antimicrobial therapy.

Lay abstract We describe the validation of an assay to analyze ceftolozane and tazobactam simultaneously in saline matrixes. This methodology represents a simple, reproducible approach to the determination of drug concentrations. This method can be modified to determine human concentrations of this antibiotic, which would be important for doctors to determine appropriate patient dosing.

Keywords::

• BAL
• ceftolozane
• HPLC–MS
• tazobactam

Author contributions

CA Sutherland prepared samples, analyzed data and prepared the manuscript. C Ozbal analyzed the samples and prepared the manuscript. DP Nicolau acted as study director, designing the study, reviewing all data and reviewing the manuscript.

Acknowledgments

The authors would like to thank Merck & Co., Inc. for providing analytical standards.

Financial & competing interests disclosure

DP Nicolau is on the speaker bureau for Merck and has received grants from Merck. 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.