Physicochemical stability of norepinephrine bitartrate in polypropylene syringes at high concentrations for intensive care units.

OBJECTIVES: Norepinephrine is usually used in emergency situations such as in intensive care units (ICUs) for the restoration of blood pressure. The objective was to study the stability of highly-concentrated solutions of norepinephrine at 0.50mg/mL and 1.16mg/mL, diluted in glucose 5% (G5%) in polypropylene syringes, protected or not from light, up to 48h. MATERIALS AND METHODS: Chemical stability was analysed by high-performance liquid chromatography coupled to photodiode array detection at each time of the analysis. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection. Three syringes for each condition were prepared. At each time of the analysis, three samples were analysed for each syringe. pH values were evaluated at each moment of the analysis. RESULTS: Solutions of norepinephrine at 0.50 and 1.16mg/mL, diluted in G5%, with or without protection from light, retained more than 95.0% of the initial concentration after a 48-hour storage at 20-25°C. No visual and subvisual modification occured during the stability study. No degradation product appearing during the stressed degradation was observed during the study but an additional peak with a relative retention at 0.66 was observed and constant. This peak was identified as 5-hydroxymethylfurfural, a degradation product of glucose. CONCLUSION: Norepinephrine diluted in G5% at 0.50mg/mL and 1.16mg/mL was physically and chemically stable over a period of 48hours at room temperature. These stability data of highly concentrated solutions provide additional knowledge to assist intensive care services in daily practice.

First international database of research teams in stability and compatibility of medications: An additional function in the Stabilis® database.

A new function on the international database Stabilis® has been created: a database of research teams involved in stability and compatibility studies of drugs. The first part is descriptive. For each team, the list of publications and of molecules studied can be edited. A search function can extract data by using different criteria like the drug, galenic form, pharmacological class, molecule form (small molecule, monoclonal antibody), country, author and years of publications. The second part of the new function is interactive and allows Stabilis® users to suggest stability studies. After examination by collaborators of Stabilis®, the suggestions are rejected, modified or accepted, published on the website and available for all research teams. The United States of America (USA) was the main country in the 1990s but today, Europe has 67 active teams which publish stability studies and 50 for USA. Europe is now the more active zone in term of number of publications. Antibiotics and cytotoxics are the main pharmacological classes studied. Monoclonal antibodies are studied by few teams due to the complexity of the methodology to study the stability of these drugs. This database can facilitate the communication between research teams and users.