Author(s): Stepensky D, Chorny M, Dabour Z, Schumacher I
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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. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association.
This article was published in J Pharm Sci
and referenced in Journal of Developing Drugs