OBJECTIVE To establish an LC-MS/MS method for simultaneous determination of the concentration of ceftazidime-avibactam, polymyxin B and tigecycline(containing ceftazidime, avibactam, polymyxin B1, B2 and tigecycline) in human plasma.

METHODS The plasma samples(50 μL) were precipitated with methanol. Cefazolin, sulbactam, polymyxin E2 and tigecycline-d9 were used as internal standards. The chromatographic separation was performed on a Kinetex C₁₈ column(3 mm×100 mm, 2.6 μm) with gradient elution using a mobile phase of 0.1% formic acid-water(containing 5 mmol·L⁻¹ ammonium acetate solution)(A) and 0.1% formic acid-methanol(B), at a flow rate of 0.5 mL·min⁻¹. The total analysis time was 5 min. The detection of the analytes was performed by positive and negative electrospray ionization simultaneously. Multiple reaction monitoring was used with the transition of m/z 547.1→468.0(ceftazidime, +), m/z 263.9→80.0(avibactam, –), m/z 602.6→101.2(polymyxin B1, +), m/z 595.5→202.1(polymyxin B2, +), m/z 586.4→513.4(tigecycline, +).

RESULTS It was linear(r>0.995 0) over the calibration range for different analytes. The accuracy was 88.32%–110.4%. The RSD of precision was less than 15%(20% at the lower limit of quantification). The matrix effect, recovery, stability, dilution integrity and carryover met the acceptance criteria. The plasma concentrations in 54 samples from 25 patients with carbapenem-resistant organism infection were determined by this method.

CONCLUSION This method is simple and fast with good accuracy, sensitivity and stability. It is suitable for clinical therapeutic drug monitoring of ceftazidime-avibactam, polymyxin B and tigecycline, providing scientific reference for individualized medication in the treatment of carbapenem-resistant organism infection.