Abstract

A stability indicating RPLC method for aripiprazole

Author(s): D.V.Subba Rao, Satheesh Kumar Shetty, P.Radhakrishnanand, V.Himabindu

A simple, sensitive isocratic RP-LC method has been developed for the quantitative determination of aripiprazole in both bulk drug and pharmaceutical dosage forms, used as a typical antipsychotic drug. The developed method also applicable for the related substances determination. Efficient chromatographic separation was achieved on a Kromasil C8, 150mm4.6mm, 5mcolumnwith simplemobile phase combination delivered in an isocratic mode and quantification was carried out using ultraviolet detection at 215 nm with a flow rate of 1.0 mL min-1. The mobile phase contains a mixture of buffer and acetonitrile in the ratio of 65:35 (v/ v). Buffer consists of 30mMsodium dihydrogen phosphate monohydrate and 5mM hexane-1-sulfonic acid sodium salt, pH adjusted to 2.5 using phosphoric acid. In the developed HPLC method the resolution (Rs) between aripiprazole and for its potential five impurities in bulk drug was found to be greater than 2.0. Regression coefficient (r2) value of greater than 0.99 for aripiprazole and it’s all the five impurities shows good linearity of the developed method. This method was capable of detecting all five impurities of aripiprazole at a level of 0.009% with respect to test concentration of 0.5 mg mL-1 for a 5L injection volume. The inter and intraday precision for all five impurities and aripiprazole were found to be within 2.0% RSD at its specification level. The method has shown good and consistent recoveries for aripiprazole (98.4-100.6%) and for it’s all the five impurities (93.5-106.2%). The test solution was found to be stable in the diluent for 48h. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradationwas found to occur in alkaline mediumand in oxidative stress conditions. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.4%. The developed RP-LCmethod was validated with respect to linearity, accuracy, precision and robustness.