The ICH guidance in practice: Stress degradation studies on irbesartan and development of a validated stability-indicating UPLC assay

Abstract

In this research work comprehensive stress testing of irbesartan was carried out according to ICH guideline Q1A (R2), and a stability-indicating reversed-phase ultra-performance liquid chromatographic (UPLC) assay was established. The drug was subjected to acid (0.1 m HCl), neutral, and alkaline (0.1 m NaOH) hydrolytic conditions at 80°C, and to oxidative decomposition at room temperature. Photolysis was carried out by exposing the drug to sunlight (60,000–70,000 lux) for two days. The solid drug was also subjected to 50°C for 60 days in a hot-air oven. Degradation of the drug was found to occur under alkaline, acidic, and neutral hydrolytic conditions. Separation of the drug and the degradation products was successfully achieved on a BEH (bridged ethylene hybrid) C18 column with 40:60 aqueous glacial acetic acid (0.2%)-acetonitrile as mobile phase. The flow rate and detection wavelength were 0.1 mL min−1 and 229 nm, respectively. The method was validated and response was found to be linear in the drug concentration range 10–50 μg mL−1. The mean values (±RSD, %) of slope, intercept, and correlation coefficient were 32102 (± 0.0535), 1295 (± 3.02), and 0.9998 (± 0.0493), respectively. RSD in intra-day and inter-day precision studies was <1%. Recovery of the drug from a mixture of degradation products was between 99.26 and 100.01%. The method was specific to the drug, selective to degradation products, and robust. PDA purity test also confirmed the specificity of the method.