Liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of cefoperazone and sulbactam in plasma and its application to a pharmacokinetic study

A rapid and highly sensitive liquid chromatography-tandem mass spectrometric (LC–MS/MS) method for simultaneous determination of cefoperazone sodium and sulbactam sodium in human plasma was developed. The analytes and internal standard (IS), cefuroxime sodium, were extracted from human plasma via liquid–liquid extraction with ethyl acetate and separated on a Waters Xterra C18 column within 3.5 min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in selected reaction monitoring (SRM) and negative ion mode. The precursor to product ion transitions monitored for cefoperazone, sulbactam and IS were m/z 644.1 → 528.0, 232.1 → 140.0, and 423.0 → 362.0, respectively. The assay was validated in the linear range of 0.1–20 μg/mL for cefoperazone and 0.02–4 μg/mL for sulbactam. The intra- and inter-day precisions (CV%) were within 8.39% for each analyte. The recoveries were greater than 87.3% for cefoperazone and 87.2% for sulbactam. Each analyte was found to be stable during all sample storage, preparation and analytical procedures. The method was successfully applied in a pharmacokinetic study of Sulperazon injection in six hospital-acquired pneumonia (HAP) patients.