Citation

Hoffman RS, Mercurio-Zappala M, Bouchard N, Ravikumar P, Goldfrank L. Disaster Med. Public Health Prep. 2012; 6(1): 20-25.

Affiliation

Author Affiliations: Drs Hoffman and Goldfrank and Ms Mercurio-Zappala are with the New York City Poison Control Center; Dr Bouchard is with the Columbia University Medical Center, New York-Presbyterian Hospital; and Dr Ravikumar is with the Public Health Laboratories, New York City Department of Health and Mental Hygiene.

Copyright

(Copyright © 2012, Society for Disaster Medicine and Public Health, Publisher Cambridge University Press)

DOI

10.1001/dmp.2011.86

PMID

22125290

Abstract

Objectives:  Oximes such as pralidoxime (2-PAM) are essential antidotes for life-threatening organophosphate poisoning. Unfortunately, oximes are expensive, have limited use, and have short shelf lives. As such, maintaining large stockpiles in preparation for terrorist activity is not always possible. We have demonstrated that atropine is stable well beyond its labeled shelf life and that recently expired 2-PAM was clinically efficacious in a series of poisoned patients. Because 2-PAM is often dosed empirically, clinical improvement does not guarantee pharmacological stability. We therefore chose to analyze the chemical stability of expired 2-PAM. Methods:  Samples of lyophylized 2-PAM were maintained according to the manufacturer's recommendations for 20 years beyond the published shelf life. We studied 2-PAM contained in a MARK I autoinjector that was stored properly for 3 years beyond its expiration date. An Agilent LC/MSD 1100 with diode-array detector and an Agilent Sorbax SB-C-18, 4.6 × 150 mm, 5-μm column were used with the following solvent systems: water with 0.01% trifluoroacetic acid and methanol with 0.01% trifluoroacetic acid. Fresh reagent grade 2-PAM was used as a standard. Results were repeated for consistency. Results:  Lyophylized 2-PAM was a white powder that was clear and colorless in solution. Liquid chromatography was identical to the standard and resulted in 2 isolated peaks with identical mass spectra, suggesting that they are stereoisomers. The autoinjector discharged a clear, yellowish solution. In addition to the 2 peaks identified for lyophylized 2-PAM, a small third peak was identified with a mass spectra corresponding to the reported N-methyl pyridinium carboxaldehyde degradation product. Conclusions:  When properly stored, lyophylized 2-PAM appears to be chemically stable well beyond its expiration date. Although the relative amount of degradation product found in solubilized (autoinjector) 2-PAM was small, it is unclear whether this may be toxic and therefore is of concern. Further studies performed with lots of drug stored under varied conditions would be required to fully determine the stability of expired 2-PAM.

Language: en