Rachid Ousama, Simons F Estelle R, Rawas-Qalaji Mutasem, Lewis Stephen, Simons Keith J
a College of Pharmacy, Faculty of Health Sciences, University of Manitoba , Winnipeg , MB , Canada.
b Department of Pediatrics & Child Health and Department of Immunology , College of Medicine , Faculty of Health Sciences , University of Manitoba , Winnipeg , MB , Canada , and.
Drug Dev Ind Pharm. 2016 Jan;42(1):131-135. doi: 10.3109/03639045.2015.1035283. Epub 2015 May 22.
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.
We examined the epinephrine doses delivered from activated EAIs stored constantly or cyclically at 70 °C.
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.
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.
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.
通过肾上腺素自动注射器（EAIs）快速注射肾上腺素是院外环境中过敏性反应的主要治疗方法。建议在室温（25°C）下储存EAIs；然而，有时会出现温度过高的储存情况。据我们所知，此前尚无关于在这种温度下储存后EAIs喷出的肾上腺素剂量的相关报道。
我们研究了在70°C下持续或循环储存的激活EAIs喷出的肾上腺素剂量。
25支有效期内的EAIs在70°C（过热）或25°C（对照）下持续或循环储存5天或10天。激活EAIs并使用高效液相色谱-紫外检测法（HPLC-UV）测量喷出溶液中的肾上腺素剂量。还通过HPLC-UV测量肾上腺素的对映体纯度。
对照EAIs喷出的体积为0.300±0.006 mL，含标记剂量（LD）的103.7±3.3%。在70°C下持续储存5天或10天并在70°C下激活后，EAIs喷出的体积分别为0.367±0.008 mL，含96.8±3.8% LD，以及0.373±0.007 mL，含77.7±3.3% LD。在70°C下循环储存5天并在激活前冷却至25°C后，EAIs喷出的体积为0.311±0.008 mL，含87.2±1.9% LD。在本研究的实验条件下，所有EAIs的肾上腺素溶液产生的色谱峰仅代表肾上腺素的纯左旋对映体。
EAIs应在制造商推荐的条件下储存。在过高温度下储存的EAIs在仍处于高温时不能用于治疗人类，冷却后也不能依赖其在过敏性反应中提供标记的肾上腺素剂量。
