Abstract
Introduction
Epinephrine is the first-line medical treatment for anaphylaxis, a life-threatening allergic syndrome that may be triggered by an insect sting, substances, medications, and certain foods. Administering epinephrine can rapidly reverse bronchospasm and other life-threatening changes from anaphylaxis. Backcountry recreationalists and guides carry epinephrine in the form of an autoinjector. Epinephrine may be exposed to cold temperatures during these expeditions. No studies have examined the stability of epinephrine after being exposed to freezing temperatures.
Objectives
The purpose of this study was to determine whether freeze-thaw cycles alter the concentration of epinephrine and to compare these results with standards of therapeutic activity. The United States Pharmacopeia (USP) designates an epinephrine solution must contain between 90% and 115% of the labeled epinephrine amount to meet USP standards.
Methods
Epinephrine from 6 autoinjectors (Epi-Pen, Mylan Speciality, Basking Ridge, NJ) was extracted and divided into experimental and control samples. The experimental samples underwent 7 12-hour freeze cycles at an average temperature of −25.4°C followed by 7 12-hour thaw cycles at an average temperature 22.7°C. The control samples remained at an average temperature of 23.1°C for the duration of the study. Immediately after the seventh thaw cycle, epinephrine concentrations were measured using a high-performance liquid chromatography assay with mass spectrometry detection.
Results
The mean concentration of the freeze-thaw samples increased compared to the control samples: 1.07 mg/mL (SD 8.78, 95% CI: 1.04–1.11) vs 0.96 mg/mL (SD 6.8, 95% CI: 0.94–0.99), respectively (P < .01).
Conclusions
Epinephrine concentrations remain within the therapeutically active range (90% to 115%) after repetitive freeze-thaw cycles. This knowledge benefits those who must emergently administer epinephrine after the medication has accidentally frozen and then thawed.