Adrenaline quality assessment – The Israel experience
Adrenaline a chiral molecule, widely used for a number of acute medical conditions, and only L-isomer has significant pharmacological activity. Being relatively unstable, L-isomer degrades via number of pathways. Therefore, quality and potency of adrenaline injections from different vendors can be compromised, especially towards the end of their shelf-life, if substantial amount of L-adrenaline undergoes racemization to the D-enantiomer. For tens of years the Israel Defense Forces (IDF) uses adrenaline ampules of different manufacturers in the clinics and in pre-hospital field conditions. These ampoules are subjected to a dedicated stability surveillance program.
A total of 114, 13, and 21 individual batches of three different manufacturers (A,B,C) were analyzed, some of them multiple times, during and post- their shelf-life period, while being stored at room temperature.
Products A and B maintained stability for at least 24 months, while Product B L-adrenaline content remained well above 85% of the stipulated content even after 24 months of storage. The content of the pharmacologically-active L-adrenaline isomer in the Product C declined rapidly during its storage at the recommended conditions, leading to compromised potency and clinical efficacy of this drug product. This problem is apparently aggravated in austere field conditions, when medicines are exposed to non-recommended storage conditions (e.g., extremes of temperature).
The reason for the differences in the drug degradation kinetics in the studied products is not known. Further investigation is needed to reveal the factors that govern the degradation pathways of L-adrenaline in the studied drug products, and to identify the most stable formulation of this drug.
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