Impurity Profiling of a Nonsteroidal Analgesic Drug by Capillary Electrochromatography

Abstract

A method was developed using capillary electrochromatography for the profiling of synthesis impurities and degradation products of a nonsteroidal analgesic drug. Based on an existing reversed phase HPLC method, the electrochromatographic assay was optimized with regard to the mobile phase composition, buffer pH, buffer salt, buffer concentration and separation voltage. Under optimized separation conditions the main compound could be separated from six structurally related impurities within 20 minutes. Different approaches were taken to improve the sensitivity of the electrochromatographic method. As a result a limit of quantitation of 0.5 μg·mL−1 or 0.05% (w/w) could be achieved for the impurities. The method was validated according to the current ICH guidelines to demonstrate the suitability of the assay for its intended use. It was found to be linear over a range of two orders of magnitude (0.5 μg·mL−1–50 μg·mL−1). With a retention time precision of 0.9% and an injection precision of 1.9%, the capillary electrochromatographic method is comparable to the corresponding HPLC method.