Send to

Choose Destination
Chemistry. 2018 May 23;24(29):7349-7353. doi: 10.1002/chem.201801176. Epub 2018 Apr 30.

Accelerated Forced Degradation of Pharmaceuticals in Levitated Microdroplet Reactors.

Author information

Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907, USA.
Department of Analytical Sciences, MRL, Merck & Co., Inc., West Point, PA, 19446, USA.
Department of Analytical Research & Development, MRL, Merck & Co., Inc., Rahway, NJ, 07065, USA.


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.


Leidenfrost effect; forced degradation; kinetics; mass spectrometry; reaction acceleration

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center