Abstract

In this present research work, a new stability indicating assay method was developed for the estimation of trandolapril and its degraded products by isocratic reversed phase chromatographic technique using ultra performance liquid chromatography. The Study involves a comprehensive stress testing of trandolapril which was carried out according to ICH guideline Q1A (R2). The drug was subjected to acid (0.1M HCl), neutral (water) and alkaline (0.1M NaOH) hydrolysis at 80°C, as well as the drug was kept at room temperature with H2O2 for oxidative decomposition. Photolysis was carried out by exposing this drug into sunlight (60,000-70,000 lux) for 2 days. Additionally, the solid drug was subjected to 50°C for 60 days in a hot air oven for thermal degradation. The results reveal that the degradation products of this drug were found in alkaline medium, acidic conditions and also in neutral hydrolysis. Separation of this drug and its degradation products (from various stress conditions) was successfully achieved on a BEH (bridged ethylene hybrid) C18 column utilizing water-acetonitrile in the ratio of 20:80. The flow rate and the detection wavelength for the analysis were 0.2 mL/min and 215 nm, respectively. The method was validated and the response was found to be linear in this drug concentration range of 0.431-2.155 μM/mL (10 – 50 μg/mL). The mean values (± %RSD) of slope, intercept and correlation coefficient were 2674262 (±0.9), 14924 (±1.02) and 0.9999 (±0.08), respectively. The ±RSD values for intra- and inter-day precision studies were < 1% and < 2%, respectively. The recovery of this drug ranged between 98.93-100.18% from a mixture of degradation products. The obtained results reveal that the developed method is specific to this drug and selective to the degradation products.

Keywords: Trandolapril, Stress testing, Stability-indicating assay method, RP-UPLC, Stability test guideline (Q1A), ICH guideline, Degradation products, Thermal degradation, Photolysis, Oxidative decomposition