Stability of Ready-to-Administer and Ready-to-Use Epinephrine and Norepinephrine Injection Solutions

Abstract

Abstract Background In the University Medical Centre Mainz, standard concentrations are defined for medicinal products to be administered by continuous injection with syringe pumps in adult intensive care patients. The objective of this study was to evaluate the physicochemical stability of ready-to-use and ready-to-administer preparations containing Epinephrine (E) and Norepinephrine (NE) in standardized concentrations and prepared batch wise in the pharmacy department as basis for assigning shelf-lives. Methods E 20 µg/mL and NE 10 µg/mL in disposable syringes and NE 40, 100, 200, 400 µg/ml in 50 ml amber type I glass vials were prepared batch wise and the concentrations were analyzed by stability-indicating, validated reversed-phase HPLC-PDA assays. Test solutions for long-term stability studies were stored under refrigeration (2–8 °C) for 6–12 months or at elevated temperatures (21–27 °C) light protected for up to 6 months or without light protection for up to one month. Osmolality and pH were measured on predefined intervals. Results The concentrations of E in 50 mL syringes and NE in 10 mL syringes remained unchanged over a period of 6 months when stored at 2–8 °C. NE preparations of different concentrations prepared in amber glass vials remained stable over a study period of 12 months. At RT the shelf-life decreased to about 6 months and the exposure to mixed daylight at RT caused loss of stability in only few days. Conclusions Batch wise preparation of ready-to-administer (RTA) preparations containing 20 µg/mL E or 10 µg/mL NE in disposable syringes as well as ready-to-use (RTU) preparations containing 40, 100, 200 and 400 µg/mL NE was successfully implemented in a pharmacy department. Storage of the preparations at refrigerated temperatures is required to obtain acceptable shelf-lives of 6–12 months. Elevated temperatures and especially exposure to mixed daylight significantly decreased the shelf life.