Long-Term Stability Study of L-Adrenaline Injections: Kinetics of Sulfonation and Racemization Pathways of Drug Degradation

David Stepensky, Michael Chorny, Ziad Dabour, Ilana Schumacher

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Injectable formulations of L-adrenaline are commonly used in emergency medicine. Despite numerous studies, the comparative contribution and kinetics of the L-adrenaline inactivation pathways during storage have not been conclusively evaluated. We examined the kinetics of L-adrenaline degradation in a prospective study and determined the extent of drug inactivation by different pathways during and beyond the stipulated product shelf-life in 42 batches of adrenaline ampules stored under controlled conditions. The content of L-adrenaline and degradation products was determined with a chiral high-performance liquid chromatography (HPLC) assay, and the degradation products were identified by mass spectrometric detection as D-adrenaline and L- and D-adrenaline sulfonate. The kinetics of the content change with storage was analyzed simultaneously for L-adrenaline and the degradation products using kinetic modeling. The lower acceptable level of adrenaline content in the formulation stated by US Pharmacopoeia (90% as a sum of L- and D-isomers) was attained after 2.0 years of storage, at which time the content of the therapeutically active L-isomer amounted to as low as 85%. The modeling revealed significant differences in the degradation kinetics in the formulations produced before and after 1997, whose cause remained unidentified in this study.

Original languageEnglish
Pages (from-to)969-980
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume93
Issue number4
DOIs
StatePublished - 1 Jan 2004
Externally publishedYes

Keywords

  • Adrenaline
  • Chirality
  • HPLC (high-performance liquid chromatography
  • Stability

Fingerprint

Dive into the research topics of 'Long-Term Stability Study of L-Adrenaline Injections: Kinetics of Sulfonation and Racemization Pathways of Drug Degradation'. Together they form a unique fingerprint.

Cite this