Strategy for identification and characterization of small quantities of drug degradation products using LC and LC-MS: application to valsartan, a model drug.

ABSTRACT

The present study demonstrates the applicability of a strategy involving use of liquid chromatography (LC) and liquid chromatography-mass spectrometry (LC-MS) techniques for the identification and characterization of minute quantities of degradation products, without their isolation from the reaction matrix in pure form. Valsartan was used as a model drug. It was subjected to forced degradation studies under the International Conference on Harmonisation (ICH) prescribed conditions of hydrolysis (acid, base and neutral), photolysis, oxidation and thermal stress. The drug showed lability under acid/neutral hydrolytic and photolytic conditions, while it was stable to base hydrolytic, oxidative and thermal stress. Three small degradation products were formed, which were separated on a C-18 column using a gradient method. The same were characterized with the help of their fragmentation pattern and accurate masses obtained upon LC-MS/TOF analyses and online H/D exchange studies. The structures were supported by appropriate mechanistic explanation. The strategy involving use of LC and LC-MS for the identification and characterization of minute quantities of degradation products was applied on a model drug, valsartan. Three degradation products were successfully characterised without their isolation from the reaction matrix in pure form. The structures were supported by appropriate mechanistic explanation.