Long-term stability study of L-adrenaline injections: Kinetics of sulfonation and racemization pathways of drug degradation
✍ Scribed by David Stepensky; Michael Chorny; Ziad Dabour; Ilana Schumacher
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 263 KB
- Volume
- 93
- Category
- Article
- ISSN
- 0022-3549
No coin nor oath required. For personal study only.
✦ Synopsis
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.