A stability-indicating ultra-performance liquid chromatographic method for estimation of related substances and degradants in paliperidone active pharmaceutical ingredient and its pharmaceutical dosage forms.

ABSTRACT

A simple, linear gradient, rapid, precise and stability-indicating analytical method was developed for the estimation of related substances and degradants of paliperidone API and tablets. The chromatographic separations were achieved using an Acquity ultra-performance liquid chromatograph (BEH 100 mm, 2.1 mm, 1.7 µm C-18 column) employing 0.01 M potassium dihydrogen phosphate buffer (pH 2.0) as mobile phase A and acetonitrile-water (91) as mobile phase B. A linear gradient (mobile phase A, mobile phase B in the ratio of 8416) with a 0.45 mL/min flow rate was chosen. All six impurities were eluted within five minutes of run time. The column temperature was maintained at 25 °C and a detector wavelength of 238 nm was employed. Paliperidone was exposed to thermal, photolytic, hydrolytic and oxidative stress conditions. The stressed samples were analyzed by the proposed method. Considerable degradation of the analyte was observed when it was subjected to oxidative conditions and impurity F was found to be the major degradant. Peak homogeneity data of paliperidone obtained by photodiode array (PDA) detection demonstrated the specificity of the method in the presence of degradants. The method was validated with respect to linearity, precision, accuracy, ruggedness, robustness, limit of detection and limit of quantification.