Abstract: Objective To establish an LC-MS/MS method for the determination of ceftazidime (CAZ) and avibactam (AVI) in human plasma and apply the method to detection of clinical samples. Methods Plasma samples were deproteinized via methanol precipitation, with CAZ-d₆ and AVI-¹³C₅ as internal standards (IS), respectively. Chromatographic separation was performed on a ProChrom300 C₁₈ column (Pusheng Technology, 2.1 mm×50 mm, 3 μm particle size) using gradient elution with 0.1% formic acid in water and in methanol respectively. The flow rate was 0.3 mL·min^-1 and the column temperature was 40°C. For CAZ under the ESI⁺ mode, the qualitative and quantitative ion pairs were m/z 547.0>467.7 and m/z 547.0>396.0, respectively while the corresponding ion pairs for its IS were m/z 553.0>402.0 and m/z 553.0>473.7, compared with m/z 263.7>79.8 and m/z 263.7>96.0 respectively and m/z 268.7>79.8 and m/z 268.7>96.0 respectively for AVI-under ESI^-. Results CAZ showed good linearity over the range of 2.00 μg·mL^-1 to 200.30 μg·mL^-1. The intra-day and inter-day accuracies were -5.64% to 3.79% and -7.10% to -1.83%, respectively while the intra-day and inter-day precisions (RSD%) were 1.06% to 3.34% and 1.45% to 6.36%, respectively, compared with 0.21 μg·mL^-1 to 20.50 μg·mL^-1, -5.22% to 13.39% and -3.46% to 5.06%, and 2.39% to 3.88% and 2.41% to 6.23% for AVI. The recovery rates of CAZ at low, medium and high concentrations ranged from 95.00% to 98.50%, compared with 96.50% to 105.10% for AVI. Samples remained stable under all tested conditions. Conclusion The established LC-MS/MS method for the determination of plasma CAZ and AVI is accurate, stable, simple, and suitable for clinical monitoring of therapeutic drugs.

Key words: HPLC-MS/MS, Ceftazidime, Avibactam, Therapeutic Drug Monitoring, Plasma