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Preparing for Chemical Terrorism: A Study of the Stability of Expired Pralidoxime (2-PAM)

Published online by Cambridge University Press:  08 April 2013

Robert S. Hoffman ,
Maria Mercurio-Zappala ,
Nicole Bouchard ,
Padinjarekuttu Ravikumar  and
Lewis Goldfrank
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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.

(Disaster Med Public Health Preparedness. 2012;6:20–25)

Keywords

chemical poisoningterrorismpralidoximeorganophosphate poisoning2-PAMatropinestabilityshelf life
Type
Original Research
Information
Disaster Medicine and Public Health Preparedness , Volume 6 , Issue 1 , March 2012 , pp. 20 - 25
Copyright
Copyright © Society for Disaster Medicine and Public Health, Inc. 2012

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References

REFERENCES

1.Dart, RC, Borron, SW, Caravati, EM, et alAntidote Summit Authorship Group. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2009;54 (3):386–394, e1.CrossRefGoogle ScholarPubMed
2.Dart, RC, Goldfrank, LR, Chyka, PA, et alCombined evidence-based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States. Ann Emerg Med. 2000;36 (2):126–132.Google Scholar
3.Dart, RC, Stark, Y, Fulton, B, Koziol-McLain, J, Lowenstein, SR.Insufficient stocking of poisoning antidotes in hospital pharmacies. JAMA. 1996;276 (18):1508–1510.Google Scholar
4.Eddleston, M, Buckley, NA, Checketts, H, et alSpeed of initial atropinisation in significant organophosphorus pesticide poisoning—a systematic comparison of recommended regimens. J Toxicol Clin Toxicol. 2004;42 (6):865–875.CrossRefGoogle ScholarPubMed
5.Pawar, KS, Bhoite, RR, Pillay, CP, Chavan, SC, Malshikare, DS, Garad, SG.Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet. 2006;368 (9553):2136–2141.CrossRefGoogle ScholarPubMed
6.Wiens, MO, Zed, PJ, Lepik, KJ, et alAdequacy of antidote stocking in British Columbia hospitals: the 2005 Antidote Stocking Study. CJEM. 2006;8 (6):409–416.CrossRefGoogle ScholarPubMed
7.Juurlink, DN, McGuigan, MA, Paton, TW, Redelmeier, DA.Availability of antidotes at acute care hospitals in Ontario. CMAJ. 2001;165 (1):27–30.Google Scholar
8.Plataki, M, Anatoliotakis, N, Tzanakis, N, Assithianakis, P, Tsatsakis, AM, Bouros, D.Availability of antidotes in hospital pharmacies in Greece. Vet Hum Toxicol. 2001;43 (2):103–105.Google ScholarPubMed
9.Teresi, WM, King, WD.Survey of the stocking of poison antidotes in Alabama hospitals. South Med J. 1999;92 (12):1151–1156.Google Scholar
10.Woolf, AD, Chrisanthus, K.On-site availability of selected antidotes: results of a survey of Massachusetts hospitals. Am J Emerg Med. 1997;15 (1):62–66.Google Scholar
11.Schier, JG, Ravikumar, PR, Nelson, LS, Heller, MB, Howland, MA, Hoffman, RS.Preparing for chemical terrorism: stability of injectable atropine sulfate. Acad Emerg Med. 2004;11 (4):329–334.CrossRefGoogle ScholarPubMed
12.Bouchard, NC, Mercurio-Zappala, M, Abreu, EM, et alExpired 2-PAM effectively reverses cholinergic crisis in humans [abstract]. J Toxicol Clin Toxicol. 2004;42:742.Google Scholar
13.Medicis, JJ, Stork, CM, Howland, MA, Hoffman, RS, Goldfrank, LR.Pharmacokinetics following a loading plus a continuous infusion of pralidoxime compared with the traditional short infusion regimen in human volunteers. J Toxicol Clin Toxicol. 1996;34 (3):289–295.CrossRefGoogle Scholar
14.Drugs past their expiration date. Med Lett Drugs Ther. 2002;44 (1142):93–94.Google Scholar
15.Lyon, RC, Taylor, JS, Porter, DA, Prasanna, HR, Hussain, AS.Stability profiles of drug products extended beyond labeled expiration dates. J Pharm Sci. 2006;95 (7):1549–1560.Google Scholar
16.Schroeder, AC, DiGiovanni, JH, Von Bredow, J, Heiffer, MH.Pralidoxime chloride stability-indicating assay and analysis of solution samples stored at room temperature for ten years. J Pharm Sci. 1989;78 (2):132–136.Google Scholar