Development and Validation of RP -RRLC Method for Estimation of Paliperidone and Its Impurities and RP - HPLC Method for Dissolution Study of Paliparidone in Extended Release Dosage Form

Abstract

RP-RRLC method developed for estimation of Paliperidone and its Impuries for Paliperidone extended release tablet. Dissolution method developed for estimation of Paliperidone by RP-HPLC method. RP-RRLC method RP-RRLC method has shown adequate separation for Paliperidone from their associated main impurities and their degradation products. Separation was achieved on a Zorbax SB C-18, 50 mm x 4.6 mm, 1.8 μm (Agilent) column at 50°C temperature by using a mobile phase A consisting Buffer (pH 4.0) – Acetonitrile ( 95:5, %v/v ) [Buffer: 0.05M Na2HPO4 anhydrous and Ortho phosphoric acid] and Mobile phase B at a flow rate of 1.4 ml/min, and UV detection at 238 nm. In the present study, comprehensive stress testing of Paliperidone was carried out according to ICH guideline Q1A (R2). The specificity of the method was determined by assessing interference from the placebo and by stress testing of the drug (forced degradation).There were no other coeluting, interfering peaks from excipients, impurities, or degradation products due to variable stress conditions, and the method is specific for estimation of Paliperidone. The method was validated in terms of linearity, precision, accuracy, LOD, LOQ, specificity, filter study, robustness and solution stability. The linearity of the proposed method was investigated in the range of 50-150% of test concentration. (r2 = 0.9992) for Paliperidone. 0.001-0.139% of specification limit (r2 = 0.9970) for Impurity-A and 0.002-0.225% of specification limit (r2 = 0.9987) for Impurity-B. LOD and LOQ values for impurity-A are 0.01 % and 0.03 % respectively and for Impurity-B are 0.01 % and 0.03 % respectively, RP-HPLC method Tablet Dissolution Method by HPLC was developed for the estimation of Paliperidone in its dosage forms. Analysis was achieved on a YMC-AQ, 50 mm x 4.6 mm, 5 μm, column at 25°C 125 temperature by using a mobile phase consisting Buffer (pH 2.5) – Acetonitrile ( 70:30 v/v ) [Buffer: 0.05M Sodium perchlorate monohydrate in water pH adjusted to 2.5 with perchloric acid] at a flow rate of 1.0 ml/min, and UV detection at 275 nm. The developed Dissolution method was validated for linearity, precision, accuracy, specificity, robustness and solution stability. The linearity of the proposed method was investigated in the range of 50-150% of test concentration. (r2 = 1.0) for Paliperidone, Recovery was found to be 100.5 %, Method shows 0 % Interference