Forced Degradation Of Glecaprevir: Development And Validation Of Stability Indicating RP-HPLC Method And LC-MS Characterization Of Degradants

Abstract

Forced degradation studies of the drugs and drug products are vital in pharmaceutical quality management.
Glecaprevir is an antiviral drug indicated for the treatment of Chronic HCV infection treatment. Glecaprevir was
subjected to various stress (Hydrolytic, photolytic, thermal and oxidative) conditions according to the ICH
guidelines. Degradation products were characterized by the tandem mass spectrometric method. A simple
stability indicating RP-HPLC method was developed to determine Glecaprevir in the presence of its degradation
impurities. Glecaprevir is stable in thermal, oxidative, and photolytic conditions. Degradation of the drug
observed in Acid and Base hydrolytic conditions. Separation was achieved on BEH C18 column with 10mM formic
acid aqueous solution and acetonitrile (30:70 % V/V) mobile phase in isocratic elution mode. The developed LC
method is linear in the range of 20-200µg/ml. Degradation products were characterized by tandem mass
spectral studies and the fragmentation pathways were proposed from the mass spectral analysis. The developed
RP-HPLC method was validated according to the ICH guidelines.