LC and LC-MS/TOF studies on stress degradation behaviour of candesartan cilexetil.

Stress degradation studies were conducted on candesartan cilexetil under the ICH prescribed conditions of hydrolysis (acidic, basic and neutral), photolysis, oxidation and thermal stress. Maximum degradation was observed on hydrolysis, especially in the neutral condition. The drug was also degraded significantly under photolytic conditions. However, it was stable to oxidative and thermal stress. A total of eight degradation products were formed, the separation of which was successfully achieved on a C-18 column employing a gradient method. In order to characterize each degradation product, a complete mass fragmentation pathway of the drug was initially established with the help of MS(n) and MS/TOF accurate mass studies. Subsequently, degradation products were also subjected to LC-MS/TOF investigations, which resulted in their fragmentation pattern and also accurate masses. The latter helped in the elucidation of the structure of all the degradation products, which was achieved through comparison of their fragmentation pattern with that of the drug. The major product was isolated and its structure was confirmed through NMR studies. On the whole, a more comprehensive fragmentation behaviour and degradation profile of the drug was established than reported in the literature. Copyright 2009 Elsevier B.V. All rights reserved.