Original Articles
Nehal P Bhatt, Ashok B Patel,
Abstract
The stability of the drug Brexpiprazole was studied under different stress conditions like hydrolysis (acid, alkaline and neutral), oxidation, photolysis and thermal degradation as recommended by International Conference on Harmonization (ICH) guidelines. Brexpiprazole contain amine group which makes it vulnerable to oxidative degradation to give N-oxides impurity. The mass balance was found close to 95-105%. These is the only one method available for the estimation of Brexpiprazole in presence of Process and Degradant Impurity and for the Stability study of Brexpiprazole as well as characterization of its Degradation Product(N-oxide Impurity).The chromatographic separation of the drug and its impurities was achieved in a Inertsil ODS 3V (150 cm × 4.6 mm × 5 µm) column employing a isocratic elution using 20 mM Potassium hydrogen phosphate buffer at pH 6.8 in combination of Acetonitrile(50:50 v/v) at a flow rate of 1.5 mL/min and detection performed at 220 nm by RP-HPLC. Validation has been performed according to ICH guidelines. The method was validated for system suitability, linearity, precision, limits of detection and quantitation, accuracy, specificity, robustness and ruggedness. The robustness study was done for small changes in flow rate, pH of Buffer and % of ACN in mobile phase composition. Linearity range for these method was found to be 0.96 -71 µg/mL. % Recovery value of this method was 95-105%. Brexpiprazole was chemically stable in hydrolysis (acid, alkaline and neutral), photolysis and thermal degradation but unstable in oxidative degradation condition and generate N-oxide Impurity which was isolated by Preparative chromatography. Identification and structural characterization of oxidative degradation product (N-oxide Impurity) was done by LC-MS, and 1H and 13C NMR studies.