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Background: Combination therapies have gained momentum in the disease management strategies of various indications. While it is challenging and more time consuming to develop a combined analytical method, the strategy of simultaneous analysis offers significant advantages in terms of efficiency and cost-effectiveness., Results: Due to a significant difference in efficacious dose for ceftazidime and avibactam, the calibration ranges validated in this paper were set to 0.05-50 μg/ml for ceftazidime and 0.005-5.0 μg/ml for avibactam. Interday results of ceftazidime were within 8% for accuracy and 9% for precision and within 9% for both accuracy and precision of avibactam., Conclusion: A sensitive and selective LC-MS/MS method was developed for the simultaneous quantification of ceftazidime and avibactam in rat plasma.

Aim: Avibactam, a novel non-β-lactam β-lactamase inhibitor co-administrated with the β-lactam antibiotic ceftazidime, is in clinical development. The need to evaluate its PK and PD requires accurate and reliable bioanalytical methods., Methods: We describe LC-MS/MS methods for the determination of avibactam and ceftazidime in human plasma. Avibactam was extracted using weak anionic exchange solid-phase extraction and analyzed on an amide column. Ceftazidime was extracted using protein precipitation and analyzed on a C18 column. Calibration curves were established over 10-10,000 ng/ml (avibactam) and 43.8-87,000 ng/ml (ceftazidime)., Results & Conclusion: Method validation, cross-validation between three laboratories and incurred sample re-analysis demonstrated method robustness. The methods were successfully applied to multiple clinical studies.