Identification and characterization of degradation products of irbesartan using LC-MS/TOF, MS(n), on-line H/D exchange and LC-NMR.
Irbesartan was subjected to hydrolytic, oxidative, photolytic and thermal stress, according to ICH guideline Q1A (R2). The drug showed degradation only in acidic, basic and photoacidic conditions, while it was stable to other stress conditions. A total of three degradation products were formed, which were separated on a C-8 column employing a gradient HPLC method. Initially, a complete mass fragmentation pathway of the drug was established with the help of MS/TOF, MS(n) and H/D exchange studies. Subsequently, the degradation products were subjected to LC-MS/TOF and on-line H/D exchange mass studies to obtain their accurate mass, fragment pattern and number of labile hydrogens. The MS results helped to assign tentative structures to degradation products, which were verified through (1)H and 2D COSY LC-NMR experiments. The products were identified as (2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methanamine, 1-(1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methylamino)pentylideneamino)cyclopentane carboxylic acid and 2-butyl-3-(tetrazolo[1,5-f]phenanthridin-6-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one. The structures were justified by mechanisms of their formation.
Shah
Ravi P
RP
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160062, Punjab, India.
Sahu
Archana
A
Singh
Saranjit
S
D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D002853:Chromatography, Liquid; D041961:Deuterium Exchange Measurement; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D000077405:Irbesartan; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010782:Photolysis; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D013777:Tetrazoles / Q000737:chemistry*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan