Physicochemical Stability of Cefotaxime Sodium in Polypropylene Syringes at High Concentrations for Intensive Care Units

Background Cefotaxime sodium is an antibiotic used to treat severe infections such as in intensive care units (ICUs). The recommended dose of cefotaxime sodium can vary from 3 grams (g) to 24 g per day and publications have demonstrated that continuous administration of cefotaxime sodium is the preferred mode of administration. In ICUs, a minimum volume is used for patients requiring fluid restriction, leading to high concentrations of cefotaxime sodium. The objective was to study the stability of cefotaxime sodium solutions at 83.3 mg/mL and 125 mg/mL, diluted in 0.9 % sodium chloride (0.9 % NaCl) or in 5 % glucose (G5 %), stored in polypropylene syringes, after the preparation and after a 6-hour and a 12-hour storage at 20–25 °C. Methods Three syringes for each condition were prepared. At each time of the analysis, three samples for each syringe were prepared and analysed by high performance liquid chromatography (HPLC) coupled to a photodiode array detector. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection (turbidimetry by UV spectrophotometry at 350, 410 and 550 nm as recommended by the European Consensus Conference). pH and osmolality values were measured at each time of the analysis. Results For each solvent, cefotaxime sodium solutions at 83.3 mg/mL and 125 mg/mL retained more than 90 % of the initial concentration after 12 hours. During the stability study, pH values decreased slightly, the intensity of the yellow colour increased and values of absorbance increased progressively for each wavelength and each condition. An additional peak with a relative retention of 3.01 was also observed after the forced degradation gradually increased up to 4.01 % and 3.17 % of the total of surface area of the peaks present on the chromatogram after 12 hours in 0.9 % NaCl and in G5 % respectively. Conclusions In view of the results and despite the fact that solutions retained more than 90 % of the initial concentration after HPLC analysis, we propose to limit the stability of cefotaxime sodium in 0.9 % NaCl and G5 % at 83.3 and 125 mg/mL at 6 hours. These stability data of highly concentrated solutions provide an additional knowledge to assist ICUs in daily practice. This work also demonstrates that highly concentrated cefotaxime sodium solutions are physically unstable after a 6-hour storage and cannot be administered as a daily infusion.