Long-term stability study of L-adrenaline injections: Kinetics of sulfonation and racemization pathways of drug degradation Academic Article uri icon

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. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93: 969–980, 2004

publication date

  • January 1, 2004