Stability of norepinephrine infusions prepared in dextrose and normal saline solutions

Abstract

Purpose: Norepinephrine (NE) infusions are commonly used in the intensive care unit and in the operating room. Data on long term stability of NE solutions are lacking. This prospective study was designed to evaluate the stability of NE, in dextrose (5%) in water (D5W) and in normal saline (NS) solutions, for a period up to seven days. Methods: We prepared norepinephrine solutions in quadruplicate, by aseptically diluting 1 mg NE in 250 mL of D5W or NS and 4 mg NE in 250 mL of D5W or NS (final concentrations, 4 µg·mL -1 and 16 µg·mL -1 , respectively) and stored the solutions at room temperature under ambient light. We sampled the solutions, in duplicate, at times 0, 24, 48, 72, 120, and 168 hr and stored them at -80°C for later assay. Norepinephrine concentrations were measured by high-performance liquid chromatography with electrochemical detection (coefficient of variation 4.6%). Statistical analysis was done by nonparametric, repeated measures ANOVA (Friedman test). Results:There was no significant decrease in NE concentration for either, NE 4 µg·mL -1 in D5W or NS (P = 0.09 and 0.11, respectively) or for NE 16 µg·mL -1 in D5W or NS (P = 0.18 and 0.40, respectively). The ratios of NE concentration at 168 hr, compared to baseline, were 95.7% and 96.4%, for NE 4 µg·mL -1 in D5W and NS, respectively, and 104.5% and 96.4%, for NE 16 µg·mL -1 in D5W and NS, respectively. Conclusion: Norepinephrine solutions, in concentrations commonly used in the clinical setting, are chemically stable for seven days, at room temperature and under ambient light, when diluted either in D5W or NS. (P = 0,09 et 0,11, respectivement) ou pour la solution de NE à 16 µg·mL -1 dans du D5W ou du NS (P = 0,18 et 0,40, respectivement

Stability of Norepinephrine Solutions in Normal Saline and 5% Dextrose in Water

“…These results are in general agreement with all previously published studies, [5][6][7][8][9][10][11][12][13][14] which have all demonstrated the stability of norepinephrine. Of the papers published in English and reporting results obtained with stability-indicating analytical methods, 7,10-14 the study duration was relatively short, at only 24 h, 10,12,13 36 h, 7 or 7 days.…”

“…11 Both Allwood 11 and Tremblay and others 14 found that norepinephrine was equally stable in dextrose and in saline solutions, in agreement with this study but in opposition to the product monograph. 4 In this study, ANOVA revealed no difference in stability due to diluent (p = 0.06).…”

“…Several investigators have evaluated the stability of norepinephrine in solutions intended for IV administration. [5][6][7][8][9][10][11][12][13][14] The concentrations evaluated were generally 16 mg/L or lower, although Allwood 11 and Peddicord and others 13 evaluated concentrations of 40 mg/L and 64 mg/L, respectively. Most of these studies reported the percentage remaining after only 24 h, and none evaluated the effect of light.…”

Ficts and facts of epinephrine and norepinephrine stability in injectable solutions

“…Light exposure may play a certain role, but as shown by Tremblay et al, even at ambient temperature, NE solutions remain stable for 14 days when stored unprotected (Tremblay et al, 2008). Häggendal et al observed NE degradation rates of approximately 4% after 4 h in solutions stored unprotected from light and pH values above 6.0, indicating that less acidic conditions influence the stability in a non-neglectable way (Haggendal and Johnsson, 1967).…”

Evaluation of the maximum beyond-use-date stability of regular human insulin extemporaneously prepared in 0.9% sodium chloride in a polyvinyl chloride bag

“…A time point was considered stable if the mean concentration of the samples exceeded 90% of the equilibrium concentration at 6 hours 7–10…”