A HIGHLY SENSITIVE STABILITY-INDICATING UPLC METHOD FOR THE DETERMINATION OF RELATED SUBSTANCES IN IMIPENEM AND CILASTATIN FOR INJECTION

Abstract

A simple, sensitive and specific RP-UPLC method was developed for the quantification of related impurities of Imipenem and Cilastatin in liquid pharmaceutical dosage form. The chromatographic separation employs a gradient elution using a waters Sunfire C18, 75mm×3.0mm, 2.5μm columns. Mobile phase consisting of solvent A (solution containing 0.88 g of potassium dihydrogen phosphate and 0.44 g of dipotassium hydrogen phosphate per liter of water, adjusted to pH 7.0 with sodium hydroxide)and solvent B(acetonitrile) delivered at a flow rate of 0.5 ml min−1. The analytes were detected and quantified at 215nm using photodiode array (PDA) detector. The method was validated as per ICH guidelines, demonstrating to be accurate and precise (repeatability and intermediate precision level) within the corresponding linear range of known impurities of Imipenem and Cilastatin. The specificity of the method was investigated under different stress conditions, including hydrolytic, oxidative, photolytic and thermal as recommended by ICH guidelines. Robustness against small modification in pH, column oven temperature, flow rate and percentage of the mobile phase composition was ascertained. All these results provide the stability indicating capability of the method.