Development and Validation of a Stability-Indicating RP-HPLC Method for the Quantitative Determination of Risperidone in Controlled Release Tablets for Cancer-Related Psychosis Management

Abstract

Risperidone, a benzisoxazole derivative, is widely prescribed for schizophrenia and bipolar disorders. Ensuring the quality and stability of controlled-release (CR) formulations requires a precise, reliable, and stability-indicating analytical method. The present study aimed to develop and validate a robust RP-HPLC method for quantitative estimation of risperidone in CR tablets in accordance with ICH Q2(R1) guidelines Chromatographic separation was achieved on a C18 column (250 × 4.6 mm, 5 µm) using a mobile phase consisting of acetonitrile and 0.1% orthophosphoric acid (60:40, v/v) at a flow rate of 1.0 mL·min⁻¹. Detection was performed at 280 nm with an injection volume of 20 µL. The method was validated for system suitability, specificity, linearity, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ), robustness, and solution stability. Forced degradation studies were conducted under acidic, basic, oxidative, thermal, and photolytic conditions to evaluate the stability-indicating capability. isperidone was eluted at approximately 5.8 min with well-resolved, symmetrical peaks and theoretical plate counts exceeding 5000. The calibration curve was linear over the concentration range of 0.5–50 µg·mL⁻¹ (r² = 0.9996). Mean recovery values ranged from 99.1% to 101.2%, confirming accuracy. Intra-day and inter-day precision results showed %RSD below 1.5%. The LOD and LOQ were 0.15 and 0.45 µg·mL⁻¹, respectively. Minor variations in mobile-phase composition, flow rate, and wavelength did not significantly affect assay performance, demonstrating robustness. The method effectively separated risperidone from degradation products, confirming its stability-indicating nature. The validated RP-HPLC method is simple, rapid, and reproducible, suitable for routine assay, content uniformity, dissolution, and stability studies of risperidone CR tablets. Its selectivity and robustness make it applicable for quality control analysis in pharmaceutical manufacturing environments.