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3PC-008 Physicochemical stability of norepinephrine bitartrate in polypropylene syringes at high concentrations for intensive care units
  1. E D’Huart,
  2. J Vigneron,
  3. B Demoré
  1. University Hospital of Nancy, Pharmacy, Vandoeuvre Lès Nancy, France


Background Norepinephrine is usually used in emergency situations as in intensive care units (ICUs) for the restoration of blood pressure. High doses at 3–5 µg/kg/min can be used in the treatment of septic or hemorrhagic shock.

Purpose The objective was to study the stability of high concentrated solutions of norepinephrine at 0.50 mg/mL and 1.16 mg/mL, diluted in glucose 5% (G5%) in polypropylene syringes, protected or not from light, after the preparation and after a 6 hour, 24 hour and 48 hour storage at room temperature.

Material and methods Chemical stability was analysed by high-performance liquid chromatography coupled to a photodiode array detector at each time of analysis. 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). Three syringes for each condition were prepared. At each time of analysis, three samples were prepared and analysed for each syringe. pH values were evaluated at each moment of the analysis.

Results Solutions of norepinephrine at 0.50 and 1.16 mg/mL, diluted in G5%, with or without protection from light, retained more than 95% of the initial concentration after 48 hours of storage at 20°C–25°C. Solutions remained clear, without change of colour or precipitation during the study. Concerning turbidity assays, values of absorbance remained inferior to 0.010 AU. No degradation product appeared during stressed degradation was observed during the study, but an additional peak with a retention time at 3.8 min was observed and constant. This peak was equally observed on chromatograms of the G5% solution. A solution of 5-hydroxymethylfurfural (5-HMF), a degradation product of glucose, was prepared and analysed by HPLC. The retention time was also 3.8 min and the spectrum was identical. This additional peak was identified as 5-HMF.

Conclusion Norepinephrine diluted in G5% at 0.50 mg/mL and 1.16 mg/mL were physically and chemically stable over a period of 48 hours at room temperature. These stability data of highly concentrated solutions provide additional knowledge to assist ICUs in daily practice.

References and/or acknowledgements No conflict of interest.

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