Synthesis and standardisation of aceclofenac ethyl ester and aceclofenac benzyl ester as related aceclofenac impurity

Abstract

Aceclofenac is a non-steroidal anti-inflammatory drug (NSAID). This study aimed to synthesise aceclofenac ethyl ester (E impurity) and aceclofenac benzyl ester (F impurity) of the drug aceclofenac at a laboratory scale and establish impurity criteria using high-performance liquid chromatography (HPLC) to create reference substances for E and F impurities. They were synthesised through the esterification of aceclofenac and diclofenac sodium in dimethyl formamide (DMF), optimised with yields of 96 and 66%, respectively. The HPLC method was validated in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The process of determining the purity of impurities E and F was found to be system-suitable, with RSD % of all chromatographic parameters being less than 2.0% and the asymmetry factors of E and F impurities in the range of 0.8-1.5. In terms of linearity, the R values for both impurities were in the range
of 0.9995-1.0000. The intermediate precision relative standard deviation (RSD) values for E and F impurities were 0.04 and 0.001%, respectively. The recovery rate met the requirements of 98.0-102.0%. The research has developed criteria for evaluating synthetic E and F impurities. The synthesised products met the requirements for established as reference substances, with chromatographic purity determined to be 99.94 and 99.90%, respectively, in their purity forms.