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Liquid chromatography/tandem mass spectrometry study of forced degradation of azilsartan medoxomil potassium
Author(s) -
Swain Debasish,
Patel Prinesh N.,
Palaniappan Ilayaraja,
Sahu Gayatri,
Samanthula Gananadhamu
Publication year - 2015
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.7235
Subject(s) - chemistry , degradation (telecommunications) , chromatography , hydrolysis , forced degradation , mass spectrometry , tandem mass spectrometry , liquid chromatography–mass spectrometry , electrospray ionization , trifluoroacetic acid , high performance liquid chromatography , reversed phase chromatography , organic chemistry , telecommunications , computer science
Rationale Azilsartan medoxomil potassium (AZM) is a new antihypertensive drug introduced in the year 2011. The presence of degradation products not only affects the quality, but also the safety aspects of the drug. Thus, it is essential to develop an efficient analytical method which could be useful to selectively separate and identify the degradation products of azilsartan medoxomil potassium. Methods AZM was subjected to forced degradation under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions. Separation of the drug and degradation products was achieved by a liquid chromatography (LC) method using an Acquity UPLC ® C18 CSH column with mobile phase consisting of 0.02% trifluoroacetic acid and acetonitrile using a gradient method. Identification and characterization of the degradation products was carried out using LC/electrospray ionization quadrupole time‐of‐flight mass spectrometry (ESI‐QTOFMS). Results A total of five degradation products (DP 1 to DP 5) were formed under various stress conditions and their structures were proposed with the help of tandem mass spectrometry (MS/MS) experiments and accurate mass data. A common degradation product (DP 4) was observed under all the degradation conditions. DP 1, DP 2 and DP 5 were observed under acid hydrolytic conditions whereas DP 3 was observed under alkaline conditions. Conclusions AZM was found to degrade under hydrolytic, oxidative and photolytic stress conditions. The structures of all the degradation products were proposed. The degradation pathway for the formation of degradation products was also hypothesized. A selective method was developed to quantify the drug in the presence of degradation products which is useful to monitor the quality of AZM. Copyright © 2015 John Wiley & Sons, Ltd.