Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 24, Issue 29, Pages 7349-7353Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201801176
Keywords
forced degradation; kinetics; Leidenfrost effect; mass spectrometry; reaction acceleration
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Funding
- Merck Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
- Purdue University on Chemical Instrumentation [LKR161299]
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Forced degradation is a method of studying the stability of pharmaceuticals in order to design stable formulations and predict drug product shelf life. Traditional methods of reaction and analysis usually take multiple days, and include LC-UV and LC-MS product analysis. In this study, the reaction/analysis sequence was accelerated to be completed within minutes using Leidenfrost droplets as reactors (acceleration factor: 23-188) and nanoelectrospray ionization MS analysis. The Leidenfrost droplets underwent the same reactions as seen in traditional bulk solution experiments for three chemical degradations studied. This combined method of accelerated reaction and analysis has the potential to be extended to forced degradation of other pharmaceuticals and to drug formulations. Control of reaction rate and yield is achieved by manipulating droplet size, levitation time and whether or not make-up solvent is added. Evidence is provided that interfacial effects contribute to rate acceleration.
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