Stability of Norepinephrine Solutions: DISCUSSION
Based on the fastest degradation rate observed, with 95% confidence, this study has demonstrated that solutions of norepinephrine, diluted in NS or D5W to a concentration of 64.5 mg/L and stored for 60 days with protection from light at 4°C and then at room temperature for an additional 24 h, will retain more than 95% of the initial concentration. Solutions that are not protected from light will retain only 90% of the initial concentration with storage for 39 days at 4°C. This storage period could include up to 24 h of storage at room temperature, without protected from light.
These results are in general agreement with all previously published studies, which have all demonstrated the stability of norepinephrine. Of the papers published in English and reporting results obtained with stability-indicating analytical methods, the study duration was relatively short, at only 24 h, 36 h, or 7 days. Study duration was not actually specified by Newton and others but can be inferred from data presented in the report. Similarly, study duration was not specifically mentioned by Allwood, but appears to have been 30 days. The time to achieve 90% of initial concentration was reported as 104 days for a 7.17 mg/L solution and as 114 days for a 16 mg/L solution or 174 days for a 40 mg/L solution protected from light. Although the data suggested stability for a period in excess of 100 days, Allwood recommended a shelf-life of only 30 days, a conclusion that may be constrained by the unspecified study duration in that study. Both All- wood and Tremblay and others found that norepinephrine was equally stable in dextrose and in saline solutions, in agreement with this study but in opposition to the product monograph. In this study, ANOVA revealed no difference in stability due to diluent (p = 0.06). Although some might consider this a “trend”, we would point out that the time to achieve 90% of the initial concentration (10% loss) was 26.9 days with D5W solutions stored without protection from light at room temperature but 28.7 days for the saline solution stored under similar conditions. This nonsignificant difference actually “trends” in the opposite direction from the statements in the product monograph. The product monograph4 also indicates that norepinephrine should be protected from light, and we observed that light was the single most significant factor affecting stability, whereas temperature and diluent had no such effect on stability. None of the previously published studies evaluated the effect of light.
We conclude that a 61-day expiry date is suitable for 64.5 mg/L solutions of norepinephrine in D5W or NS, when stored at 4°C with protection from light. This expiry date allows for up to 24 h storage at 23°C. The expiry dates reported in this study should be used only after due consideration of sterility and the contamination rate in any particular IV additive program.