title: Preparing for chemical terrorism: stability of injectable atropine sulfate.
abstract: OBJECTIVE
  A massive nerve agent attack may rapidly deplete in-date supplies of atropine. The authors considered using atropine beyond its labeled shelf life. The objective was to determine the stability of premixed injectable atropine sulfate samples with different expiration dates.
  
  
  METHODS
  This was an in-vitro study using gas chromatography and mass spectrometry (GC/MS). Four atropine solutions (labeled concentration of 400 microg/mL) ranging from in date to 12 years beyond expiration (exp) and an additional sample of atropine sulfate (labeled concentration of 2,000 microg/mL) obtained from a World War II era autoinjector were assayed for atropine stability. Standards of atropine sulfate and tropine were prepared and quantified by GC/MS. Study samples were prepared by adding a buffer solution to free the base, extracting with an isopropanol/methylene chloride mixture and followed by evaporating the organic layer to dryness. Pentafluoropropionic anhydride and pentafluoropropanol were then added as derivatization reagents. Study samples were heated, the derivitization reagents were evaporated, and the remaining compound was reconstituted in ethyl acetate for injection into the GC/MS.
  
  
  RESULTS
  All solutions were clear and colorless. Atropine concentrations were as follows: in date, 252 microg/mL; 2001 exp, 290 microg/mL; 1999 exp, 314 microg/mL; 1990 exp, 398 microg/mL; and WW II specimen, 1,475 microg/mL. Tropine was found in concentrations of <10 microg/mL in all study samples.
  
  
  CONCLUSIONS
  Significant amounts of atropine were found in all study samples. All samples remained clear and colorless, and no substantial amount of tropine was found in any study sample. Further testing is needed to determine clinical effect.
authors.affiliation: NYC Poison Control Center, New York, NY, USA. jschier@cdc.gov
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Schier
authors.forename: Padinjarekuttu R
authors.initials: PR
authors.lastname: Ravikumar
authors.forename: Lewis S
authors.initials: LS
authors.lastname: Nelson
authors.forename: Michael B
authors.initials: MB
authors.lastname: Heller
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Howland
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hoffman
mesh_terms: D000931:Antidotes / Q000737:chemistry / Q000600:supply & distribution; D001285:Atropine / Q000032:analysis / Q000737:chemistry*; D002021:Buffers; D002619:Chemical Warfare Agents; D004355:Drug Stability; D004356:Drug Storage; D008401:Gas Chromatography-Mass Spectrometry; D012996:Solutions / Q000592:standards; D023481:Terrorism / Q000517:prevention & control*; D014326:Tropanes / Q000032:analysis
chemical_list: D000931:Antidotes; D002021:Buffers; D002619:Chemical Warfare Agents; D012996:Solutions; D014326:Tropanes; D001285:Atropine; C005864:tropine