RT Journal Article
SR Electronic
T1 Degradation of obidoxime chloride solution for injection upon long- term storage under field conditions of Mediterranean climate vs the controlled environment
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2022.012792
DO 10.5731/pdajpst.2022.012792
A1 Itin, Constantin
A1 Zur, Meital
A1 Gorenbein, Pavel
YR 2024
UL http://journal.pda.org/content/early/2024/01/30/pdajpst.2022.012792.abstract
AB Obidoxime Chloride is an antidote for nerve gas intoxication. As an emergency medicine, it is being stored by the Israel Defense Forces (IDF) scattered through the country of Israel in depots without a controlled environment (field conditions), thus exposed to high and fluctuating temperatures. These conditions do not meet the manufacturer′s requirements. In addition, due to possible supply shortages, the utilization of expired batches was suggested. Current work investigated these matters. Long-term (15 years) storage under different conditions was initiated. Chemical stability and toxicity in rats were assessed. No difference was found between field conditions vs the controlled environment. Obidoxime assay remained >95 % for 5 years and >90 % for seven years. pH remained above the lower specification limit for seven – eight years. The major degradation product – 4-pyridinealdoxime, surpassed the allowed limit at five years. The content of total unknown impurities reached its maximum allowed by the IDF limit at four – five years. 3-fold higher than clinically utilized doses of valid-to-date Toxogonin batches administered to rats did not cause any abnormality. However, expired batches produced significant toxic effects. While no difference was found between storage of obidoxime ampoules adhering to manufacturer′s recommendations vs field conditions, accumulation of degradants over the allowed by the IDF limit at four – five years of storage and the toxicity of the expired batches observed in rats brought the IDF to a decision of shortening the shelf-life of this product from five to four years when stored in an uncontrolled environment of the Mediterranean climate.