Development and validation method for the determination of related substances in nimesulide granules for oral suspension

Abstract

One of the key stages of pharmaceutical development is the development of analytical methods for quality control of medicines. The critical quality indicator is the content of related impurities, which may increase during shelf life of the product due to the degradation of the active substance, which in turn affects the quality of the product. The aim of the work is to develop and validate the method for the determination of related impurities in nimesulide granules for oral suspension by HPLC method; to set the specification of finished product for related impurities. Materials and methods. Sample of finish product Nimesulide, granules for oral suspension, 100 mg/2 g, it was manufactured by JSC “Farmak”. The study was performed using Agilent 1260 liquid chromatograph with UV detector. 2-phenoxyaniline from Sigma-Aldrich, reference standards of nimesulide impurity D EP CRS and LGC, Nimesulide for peak identification EP CRS were used for preparation of standard impurity solutions. Acetonitrile and ammonium dihydrogen phosphate from Sigma-Aldrich were used for chromatographic analysis. Results. When developing method, the concentrations of solutions, the method of dissolving granules, filters were selected. The chromatographic column was selected, the requirements for the chromatographic system suitability were set. The effect of placebo components has been studied and considered. During the validation the characteristics were studied: specificity, linearity, LOD, LOQ, precision, accuracy, robustness. The limits of the impurity content were established in accordance with the requirements of ICH Q3B guideline, taking into account the data of stress studies, stability and impurities of the substance. Conclusions. The analytical method for the determination of related substances in finish product nimesulide granules for oral suspension was developed. The validation results showed that the method is suitable for analysis. The specification limits of finished product for related impurities were set.