ASSAY METHODS OF SULBACTAM AND CEFOPERAZONE IN BODY FLUIDS AND TISSUES

Abstract

Concentrations of sulbactam (SBT) and cefoperazone (CPZ) in body fluids and tissues following an intravenous administration of the combination of SBT/CPZ were measured by microbiological assay, gas chromatography (GC) and gas chromatograph-mass spectrometry (GC-MS).
CPZ could be determined by a standard agar-diffusion microbiological assay using Micrococcusluteus ATCC 9341 without any influence of co-existing SBT. SBT was microbiologically assayed by using a β-lactamase producing strain, Escherichia coli 603, in the presence of subinhibitory concentrations of CPZ (150μg/ml in the medium). These microbiological assay methods of SBT and CPZ revealed good sensitivity; 1.6 and 0.4μg/ml, respectively, with wide range linearity.
In addition, low concentration of SBT in biological specimens was determined by GC and GC-MS with a fairly good detection limit of 0.5μg/ml and 0.05μg/ml in the serum, respectively. The concentration of SBT in biological specimens determined by the GC method showed a good correlation with those obtained by microbiological assay method.
SBT and CPZ were stable in human serum and urine at-20°C over a period of 21 days.