(T1230-11-65) Epinephrine Degradation in Pediatric Auto-Injectors

Purpose: Epinephrine is an adrenergic medication that works on alpha and beta receptors and is used in the treatment of shock, specifically anaphylaxis. Epinephrine auto-injectors (EAIs) are used as the first-line treatment for life-threatening allergic reactions. EAIs are becoming more common within the community, due to allergies as well as vaccination programs at retail pharmacies. EAIs are dated with a relatively short expiration date, sometimes as little as 18 months from production. Due to the high cost and the short lifespan of EAIs with the manufacturer’s expiration date, we looked at ways to extend their shelf life by studying how quickly the drug degrades.

Methods: Epinephrine is a chiral molecule where only the L(-) configuration demonstrates biological activity, and the D(+) configuration is not considered biologically active. Inactive epinephrine (D-form) is present as an impurity or formed as a byproduct of active epinephrine degradation. This project utilized a chiral HPLC method to analyze the active epinephrine remaining in previously expired autoinjectors. Chiral separation of the enantiomers was performed on an ORpak CDBS-453 4.6 x 150 mm chiral column (Shodex) using an Agilent HPLC.

Results: The chiral separation technique offers good selectivity and low limits of quantification. Each sample was examined over a 20-minute run and the peaks for L(-) and D(+) epinephrine appear around 7.75 minutes and 8.23 minutes, respectively. The chiral HPLC chromatogram peak areas for each enantiomer were used to calculate the corresponding concentrations. The EAIs used in this project were collected through donation boxes placed throughout the community, including at allergy clinics and retail pharmacies. A total of 155 autoinjectors were collected and analyzed between 2018 and 2021. Adult and pediatric autoinjectors (0.3 mg and 0.15 mg, respectively) from multiple manufacturers were analyzed. The result showed that 93% of 0.3 mg (adult) doses retained 90% of active epinephrine compared with 66% of 0.15 mg (pediatric) doses within the first 36 months after expiration dating assigned by the manufacturers (Figure 1).

Conclusion: Retaining more than 90% of active medication allows the product to be deemed in-date by the FDA and is an important data point in this project. Interestingly, this project revealed that the 0.15 mg dosages seem to degrade at a more rapid pace than the 0.3 mg dosages.

References: 1. F. E. R. Simons, K. J. Simons, Epinephrine (adrenaline) in anaphylaxis. Chem Immunol Allergy 95, 211-222 (2010).
2. S. H. Sicherer, F. E. R. Simons, I. Section on Allergy and, Self-injectable Epinephrine for First-Aid Management of Anaphylaxis. Pediatrics (Evanston) 119, 638-646 (2007).
3. A. N. Pepper, Westermann-Clark, Emma, R. F. Lockey, The High Cost of Epinephrine Autoinjectors and Possible Alternatives. Journal of Allergy and Clinical Immunology: In Practice 5, 665-668.e661 (2017).
4. L. Kassel, C. Jones, R. Turin, M. Daly, A. Mengesha, Enantiomeric degradation of epinephrine in autoinjector products. J Allergy Clin Immunol Pract 10, 2463-2465.e2461 (2022).
5. D. B. K. Golden et al., Anaphylaxis: A 2023 practice parameter update. Annals of allergy, asthma, & immunology 132, 124-176 (2024).