Validated liquid chromatographic determination of a novel ACE inhibitor in the presence of its hydrolytic and oxidative degradation products as per ICH guidelines

Abstract

Imidapril hydrochloride (IMD) is a recently developed prodrug-type angiotensin-converting enzyme (ACE) inhibitor. Due to its instability under both hydrolytic and oxidative conditions, development of rapid, simple and sensitive methods for its determination in the presence of its possible degradation products is essential. We proposed two simple liquid chromatographic methods associated with ultraviolet detection. The first method is an HPTLC-densitometric one in which separation of IMD from its degradation products was achieved followed by densitometric scanning at 220 nm using silica gel F254 plates and chloroform:ethanol:acetic acid (3:0.5:0.1, v/v/v) as the developing system. The second method was based on RP-HPLC in which the separation was performed using C18 analytical column and isocratic elution system with acetonitrile: 0.15% triethylamine (pH=2.2) (40:60, v/v). The optimum flow rate was 1.5 mL min(-1) and the detection was at 220 nm. Validation was conducted in compliance with the ICH guidelines and the methods were successfully applied for IMD determination in its commercial tablets. The obtained results were statistically compared to those obtained by applying reported HPLC method where no significant difference was found in accordance with accuracy and precision.