Stability of epinephrine at standard concentrations
Roxane R Carr1, Diane Decarie2, Mary H H Ensom3
1, BSc(Pharm), ACPR, PharmD, FCSHP, BCPS, is Clinical Coordinator in the Department of Pharmacy, Children's and Women's Health Centre of British Columbia, and Assistant Professor, part-time, with the Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia.
Insights
Epinephrine solutions in dextrose are stable for 30 days at standard concentrations, whether refrigerated or at room temperature. This stability supports premixing for improved pediatric care, though further clinical studies are recommended.
Area of Science:
- Pharmacology
- Pharmaceutical Science
- Pediatric Critical Care
Background:
- Standardized medication concentrations are crucial for minimizing errors in pediatric continuous infusions.
- Premixing epinephrine, a key treatment for pediatric septic shock, can enhance safety, timeliness, and cost-effectiveness.
- Limited data exists on the stability of epinephrine at standard concentrations used in pediatric care.
Purpose of the Study:
- To assess the stability of epinephrine in 5% dextrose in water at standard concentrations.
- To determine the extended expiration date for epinephrine infusion bags stored at 4°C and 25°C for up to 30 days.
Main Methods:
- Epinephrine solutions at three standard concentrations (25, 50, 100 μg/mL) were prepared in 5% dextrose in water.
- Infusion bags were stored at 4°C and 25°C, with physical characteristics monitored daily and then every 1-5 days up to 30 days.
- High-performance liquid chromatography was used to analyze epinephrine concentration, with stability defined as ≥90% of initial concentration.
Main Results:
- No significant changes in pH, color, or precipitate were observed in any epinephrine solutions over 30 days at either temperature.
- All epinephrine formulations retained over 95% of their initial concentration at day 30.
- The 95% confidence interval indicated that at least 93% of the initial epinephrine concentration remained on day 30.
Conclusions:
- Epinephrine preparations in 5% dextrose in water are stable for up to 30 days, irrespective of refrigeration.
- The demonstrated stability supports the potential for premixed epinephrine in standard concentrations for pediatric use.
- Future clinical research is recommended to evaluate the pharmacokinetics and pharmacodynamics of these stable epinephrine formulations.
Background:
To minimize medication errors, standard concentrations are recommended for medications intended for continuous infusion in pediatric patients. Premixing of epinephrine (commonly used to manage septic shock in children) would improve timeliness, safety, and cost-effectiveness. However, information about the stability of epinephrine at standard concentrations is limited.
Objectives:
To evaluate the stability of epinephrine in 5% dextrose in water at standard concentrations and to extend its expiration date after storage in infusion bags at 4°C and 25°C for up to 30 days.
Methods:
A total of 6 infusion bags were prepared with 200 mL of epinephrine solution, 2 bags for each of 3 standard concentrations (25, 50, and 100 μg/mL). Three bags (one for each concentration) were stored under refrigeration (4°C), and the remaining 3 bags were stored at room temperature (25°C). Physical characteristics (including pH, colour, and presence of precipitate) were evaluated daily for the first 14 days and every 1 to 5 days thereafter until day 30. Three 1.5-mL samples were collected from each bag immediately after preparation (time 0), every 24 h (at 24 h, 48 h, 72 h, 96 h, etc.) for the first 14 days, and every 1 to 5 days thereafter until day 30. Each sample was analyzed by stability-indicating high-performance liquid chromatography. A solution was considered stable if it maintained at least 90% of its initial concentration.
Results:
No notable changes in pH, colour, or precipitation were observed in any of the solutions after storage at 4°C or 25°C for up to 30 days. All formulations maintained more than 95% of the initial epinephrine concentration on day 30. In addition, the calculated lower limit of the 95% confidence interval indicated that 93% or more of the initial concentration remained on day 30.
Conclusions:
Preparations of epinephrine were stable for up to 30 days, with or without refrigeration. Because stability alone does not guarantee bioavailability or efficacy of a drug, future clinical studies are recommended to evaluate the pharmacokinetics and pharmacodynamics of these formulations.
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