Stability Study and Simultaneous Determination of Norepinephrine, Moxifloxacin, and Piperacillin + Tazobactam Mixtures Applied in Intensive Care Medicine

Background: In intensive care units intravenous medicine may be used in simultaneous infusion in the same intravenous site. Sometimes, the physical compatibility and stability of the combined solutions are unknown. Objective: The objective was to develop, optimize and validate a simple, fast and sensitive stability- indicating high-performance liquid chromatography (HPLC) for simultaneous quantification of binary mixtures of norepinephrine, piperacillin + tazobactam, moxifloxacin for intravenous (IV) administration in different diluents and physical compatibility with mannitol. Methods: The HPLC method was performed on a C18LUNA (4.6x250 mm 5-Micron) column, using acetonitrile: methanol: phosphate buffer pH 3.0 (20:30:50) as eluent and validated according to ICH guidelines and applied to mixtures of norepinephrine, moxifloxacin, piperacillin, tazobactam and mannitol at 0, 2, 6, 9 and 24 h. The substances and their mixtures were also evaluated by visual inspection and pH over time. Results: The analytical method developed was specific, linear, precise, accurate and robust. No visual changes were observed in the mixtures over time, maintaining the pH values (except for piperacillin + tazobactam which changed 0.5 in 24 h) and losses of less than 10% of content over the 24 h under analyzed conditions. Conclusion: The proposed method is suitable for simultaneous analysis of norepinephrine, moxifloxacin, piperacillin and tazobactam. All tested mixtures were compatible and stable for up to 24h, which is an important result for increasing patient safety in clinical practice since it has not been reported in the literature yet. The method can be further investigated and used for different concentration and diluent combinations.