A VALIDATED STABILITY INDICATING UPLC METHOD FOR SIMULTANEOUS DETERMINATION OF ASSAY, RELATED SUBSTANCES, AND DEGRADATION PRODUCTS OF PALIPERIDONE PALMITATE ACTIVE PHARMACEUTICAL INGREDIENT AND ITS PHARMACEUTICAL INJECTION FORMS

Abstract

A simple, sensitive, and reproducible ultra-performance liquid chromatography (UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of Paliperidone palmitate in API and pharmaceutical injectable forms. The method is applicable to the quantification of related substances and assay of Paliperidone palmitate. Chromatographic separation was achieved on Acquity UPLC BEH (50 mm, 2.1 mm, and 1.7 µm) C-18 column, and the impurities are eluted with a gradient program of runtime about 10.0 min. The eluted compounds were monitored at 238 nm, the flow rate was 0.5 mL/min, and the column oven temperature was maintained at 35°C. The resolution of Paliperidone palmitate and eight (potential, bi-products and degradation) impurities was greater than 2.0 for all pairs of components. The high correlation coefficient (r2 > 0.999) values indicated clear correlations between the investigated compound concentrations and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by RSD, were less than 10.0%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method expressed as relative error was satisfactory. The drug was subjected to the International Conference on Harmonization (ICH) prescribed hydrolytic, oxidative, photolytic, and thermal stress conditions. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness, and robustness.