title: The Impact of Freeze-Thaw Cycles on Epinephrine.
abstract: OBJECTIVE
  Epinephrine is the first-line medical treatment for anaphylaxis, a life-threatening allergic syndrome. To treat anaphylaxis, backcountry recreationalists and guides commonly carry epinephrine autoinjectors. Epinephrine may be exposed to cold temperatures and freezing during expeditions. An epinephrine solution must contain 90% to 115% of the labeled epinephrine amount to meet United States Pharmacopeia standards. The purpose of this study was to determine whether freeze-thaw cycles alter epinephrine concentrations in autoinjectors labeled to contain 1.0 mg/mL epinephrine. A further objective was to determine whether samples continued to meet United States Pharmacopeia concentration standards after freeze-thaw cycles.
  
  
  METHODS
  Epinephrine from 6 autoinjectors was extracted and divided into experimental and control samples. The experimental samples underwent 7 consecutive 12-hour freeze cycles followed by 7 12-hour thaw cycles. The control samples remained at an average temperature of 23.1°C for the duration of the study. After the seventh thaw cycle, epinephrine concentrations were measured using a high-performance liquid chromatography assay with mass spectrometry detection.
  
  
  RESULTS
  The mean epinephrine concentration of the freeze-thaw samples demonstrated a statistically significant increase compared with the control samples: 1.07 mg/mL (SD ± 8.78; 95% CI, 1.04 to 1.11) versus 0.96 mg/mL (SD ± 6.81; 95% CI, 0.94 to 0.99), respectively. The maximal mean epinephrine concentration in the experimental freeze-thaw group was 1.12 mg/mL, which still fell within the range of United States Pharmacopeia standards for injectables (0.90 to 1.15 mg/mL).
  
  
  CONCLUSIONS
  Although every attempt should be made to prevent freezing of autoinjectors, this preliminary study demonstrates that epinephrine concentrations remain within 90% to 115% of 1.0 mg/mL after multiple freeze-thaw cycles.
authors.affiliation: University of Utah School of Medicine (Ms Beasley), Salt Lake City, UT. Electronic address: heather.beasley@hsc.utah.edu.
authors.forename: Heather
authors.initials: H
authors.lastname: Beasley
authors.affiliation: Division of Emergency Medicine (Drs Ng and McIntosh), University of Utah Health Care, Salt Lake City, UT.
authors.forename: Pearlly
authors.initials: P
authors.lastname: Ng
authors.affiliation: St. John's Medical Center (Drs Wheeler and Smith), Jackson, WY.
authors.forename: Albert
authors.initials: A
authors.lastname: Wheeler
authors.affiliation: St. John's Medical Center (Drs Wheeler and Smith), Jackson, WY; WWAMI Clinical Faculty (Dr Smith), University of Washington School of Medicine, Seattle, WA.
authors.forename: William R
authors.initials: WR
authors.lastname: Smith
authors.affiliation: Division of Emergency Medicine (Drs Ng and McIntosh), University of Utah Health Care, Salt Lake City, UT.
authors.forename: Scott E
authors.initials: SE
authors.lastname: McIntosh
mesh_terms: D004355:Drug Stability; D004837:Epinephrine / Q000737:chemistry* / Q000592:standards; D005615:Freezing; D012646:Self Administration / Q000295:instrumentation*
chemical_list: D004837:Epinephrine
keywords: adrenaline; anaphylaxis; autoinjector; drug stability; epinephrine