OBJECTIVE To establish an LC-MS/MS method for the determination of concentration of cefoperazone/ sulbactam in human plasma, build a clinical sampling process based on its stability study, Moreover, it is utilized in the development of personalized dosing regimens for therapeutic drug monitoring.

METHODS The chromatographic column was Dimension C₁₈(2.1 mm×100 mm, 3 μm). The mobile phase was 0.1% formic acid water-acetonitrile. The elution method and detection column temperature were gradient elution and 40 ℃. Plasma samples were precipitated by acetonitrile, and the supernatant was diluted with water before injection for analysis. Analysis was set up by multi-reaction monitoring mode and electrospray ionization. The detection ion pair of cefoperazone, sulbactam, ceftazidime(internal standard) and tazobactam were m/z 646.00→143.15, m/z 232.00→140.20, m/z 574.00→468.05, and m/z 298.90→138.15, respectively. The stability of cefoperazone/ sulbactam in whole blood sample at different temperatures were investigated.

RESULTS The linear ranges of plasma concentrations of cefoperazone/sulbactam were 0.070−32.00 μg·mL⁻¹ and 0.15−64.00 μg·mL⁻¹, respectively. The intra-day and inter-day precision RSD of low, medium and high quality control samples were all less than 15%, and the matrix effects were 100.78%–107.73% and 97.55–110.28%, respectively. The extraction recoveries were 89.70%–102.71% and 94.26%–104.70%, respectively. Cefoperazone/sulbactam were stable in heparin sodium blood collection tubes at 23 °C for 24 h and 4 °C for 48 h, which was better than the same conditions in EDTA-K2 blood collection tubes(4 h and 12 h of stability).

CONCLUSION  The LC-MS/MS method developed for the simultaneous determination of cefoperazone/sulbactam exhibits high sensitivity, accuracy, and reproducibility, thereby meeting the requirements for clinical plasma sample testing.