Development and Validation of RPLC Method for Estimation of Related Substances and Stress Degradants in Paliperidone Active Pharmaceutical Ingredient

Abstract

A new, simple, sensitive, precise, accurate and rapid Reversed Phase Chromatography (RP-HPLC) method has been developed and validated for determination and quantification of paliperidone and its related compounds in bulk drug. The separation was accomplished on Kromasil C18 (150x4.6mm, 5μm) column under gradient elution of phosphate buffer: acetonitrile: methanol (80:2:18) (mobile phase A) and phosphate buffer: acetonitrile: methanol (40:50:10) (mobile phase B) at flow rate of 1mL/min. The column temperature was maintained at 35°C and injection volume was 20μL. Photo diode array detector, set at 240nm was used for detection of drug and related compounds. 0.14% related compound C was found to be present in paliperidone API. Forced degradation of paliperidone under acidic, basic, thermal and photo condition was carried out as per ICH guideline Q1A(R2) and Q1B to demonstrate stability indicating capability of the method. Paliperidone was found to be stable in acidic, thermal and photolytic conditions. Degradation of drug was found in basic and oxidative conditions. The method was validated as per ICH Guideline Q2 (R1) for specificity, linearity, accuracy, precision, robustness, system suitability.