title: Epinephrine doses delivered from auto-injectors stored at excessively high temperatures.
abstract: BACKGROUND
  Prompt injection of epinephrine (adrenaline) from epinephrine auto-injectors (EAIs) is the primary treatment for anaphylaxis in out-of-hospital settings. Storage of EAIs at room temperature (25 °C) is advised; however, storage at excessively high temperatures sometimes occurs. To our knowledge, there are no previous publications on the doses of epinephrine ejected from EAIs after storage at such temperatures.
  
  
  OBJECTIVE
  We examined the epinephrine doses delivered from activated EAIs stored constantly or cyclically at 70 °C.
  
  
  METHODS
  Twenty-five in-date EAIs were stored constantly or cyclically at 70 °C (excessive heat) or 25 °C (controls) for 5 d or 10 d. EAIs were activated and the epinephrine doses in the ejected solutions were measured using HPLC-UV. The enantiomeric purity of epinephrine was also measured by HPLC-UV.
  
  
  RESULTS
  Control EAIs ejected a volume of 0.300 ± 0.006 mL containing 103.7 ± 3.3% of labeled dose (LD). After 5 d or 10 d of constant storage at 70 °C and activation at 70 °C, EAIs ejected a volume of 0.367 ± 0.008 mL containing 96.8 ± 3.8% LD and 0.373 ± 0.007 mL containing 77.7 ± 3.3% LD, respectively. After 5 d of cyclic storage at 70 °C and cooling to 25 °C before activation, EAIs ejected a volume of 0.311 ± 0.008 mL containing 87.2 ± 1.9% LD. Under the experimental conditions of this study, the resultant chromatographic peaks of epinephrine solutions from all EAIs represented only the pure l-enantiomer of epinephrine.
  
  
  CONCLUSIONS
  EAIs should be stored under recommended conditions of the manufacturer. EAIs stored at excessively high temperatures cannot be used to treat humans while still hot, and when cooled, cannot be relied on to deliver the labeled epinephrine dose in anaphylaxis.
authors.affiliation: a College of Pharmacy, Faculty of Health Sciences, University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Ousama
authors.initials: O
authors.lastname: Rachid
authors.affiliation: b Department of Pediatrics & Child Health and Department of Immunology , College of Medicine , Faculty of Health Sciences , University of Manitoba , Winnipeg , MB , Canada , and.
authors.forename: F Estelle R
authors.initials: FE
authors.lastname: Simons
authors.affiliation: c Health Professions Division , College of Pharmacy, Nova Southeastern University , FL , USA.
authors.forename: Mutasem
authors.initials: M
authors.lastname: Rawas-Qalaji
authors.affiliation: a College of Pharmacy, Faculty of Health Sciences, University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lewis
authors.affiliation: a College of Pharmacy, Faculty of Health Sciences, University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Simons
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy; D004355:Drug Stability; D004356:Drug Storage; D004837:Epinephrine / Q000008:administration & dosage* / Q000627:therapeutic use; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D007267:Injections / Q000295:instrumentation*; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D019999:Pharmaceutical Solutions; D004837:Epinephrine
keywords: Adrenaline; anaphylaxis; auto-injector; degradation; epinephrine; excessive temperature; stability; storage