Interaction of aztreonam with nafcillin in intravenous admixtures

Abstract

An interaction between aztreonam and nafcillin sodium in 0.9% sodium chloride injection or 5% dextrose injection stored in glass or plastic containers is reported. During preliminary experiments, admixtures of aztreonam 10 or 20 mg/mL and nafcillin sodium 10 or 20 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection prepared in glass flasks became cloudy and showed evidence of a fine precipitate. Drug concentrations were measured with a stability-indicating high-performance liquid chromatographic (HPLC) assay. Admixtures of aztreonam 20 mg/mL and nafcillin sodium 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection were prepared in polyvinyl chloride bags and stored at room temperature (23-25 degrees C) for 48 hours. The admixtures were assayed at 0, 24, and 48 hours with the same HPLC procedure used during the pretesting experiments. The precipitates were isolated, washed, and centrifuged; the supernatant was analyzed by HPLC assay, and the final residue was analyzed by nuclear magnetic resonance (NMR) spectroscopy. The initial recoveries of drug from the pretesting experiments ranged from 99.2 to 102.4%. Analysis of the precipitates indicated that the precipitate was neither a salt nor a complex formed by the physical interaction of aztreonam and nafcillin sodium, but probably a high-molecular-weight polymer formed by the covalent bonding of subunits of the formulation components. Substantial losses of both drugs from the admixtures were evident after 48 hours of storage. The precipitate was observed sooner in the admixtures containing 0.9% sodium chloride injection than in the admixtures prepared in 5% dextrose injection.(ABSTRACT TRUNCATED AT 250 WORDS)