Contamination of injectable solutions with 2-mercaptobenzothiazole leached from rubber closures

J Pharm Sci. 1983 Nov;72(11):1302-5. doi: 10.1002/jps.2600721117.


An impurity, discovered in a sample of digoxin injectable solution commercially packaged in a syringe for single-dose delivery, was found to originate from the rubber closure of the syringe and was identified as 2-mercaptobenzothiazole, a common accelerator for rubber vulcanization. Several similarly packaged injectable solutions of a variety of drugs from various manufacturers were examined and over half contained 2-mercaptobenzothiazole. The compound was identified by UV spectrophotometry (including a pH-dependent shift in its absorbance maximum), by mass spectrometry, and by comparison with standard 2-mercaptobenzothiazole using silica gel and reverse-phase high-performance liquid chromatography (HPLC). The presence of this impurity in injectable solutions may have implications with regard to toxicity and may interfere with the assay of digoxin injectable solution by HPLC.

MeSH terms

  • Benzothiazoles
  • Chromatography, High Pressure Liquid
  • Digoxin / isolation & purification
  • Drug Contamination*
  • Drug Packaging*
  • Mass Spectrometry
  • Solutions / analysis
  • Spectrophotometry, Ultraviolet
  • Thiazoles / analysis*


  • Benzothiazoles
  • Solutions
  • Thiazoles
  • captax
  • Digoxin