Analytical Method Development and Validation for Quantitative Estimation & Dissolution Study of Aripiprazole

Abstract

RRLC method was developed & validated for estimation of Aripiprazole and its Related Impuries in API & in its Orodispersible tablets. Dissolution method was developed & validated for estimation of Aripiprazole by HPLC method. RRLC method showed adequate separation for Aripiprazole 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 45°C temperature by using Methanol: Buffer (65:35 v/v) at pH 3.0 ± 0.05 using glacial ortho phosphoric acid as eluent, at a flow rate of 1.0 ml/min. Detection was carried out at 248 nm. The method was validated in terms of linearity, precision, accuracy, specificity, robustness and solution stability. The linearity of the proposed method was investigated in the range of 50-156.3% of test concentration. (r = 0.9995) for Aripiprazole, Specificity of the method was established by determining the peak purity of the peaks of the drugs in a stress samples using PDA detector. Placebo preparation was also analyzed for specificity. The method was found to be rugged and precise within the linearity range. The related impurities were separated using a gradient system using the mixture of Buffer: ACN as mobile phase [Mobile phase-A: (90:10 %v/v) and Mobile phase-B: (20:80 %v/v)] at pH 3.2 ± 0.05 using glacial ortho phosphoric acid as eluent, at a flow rate of 1.0 ml/min. Detection was carried out at 248 nm. The linearity of the proposed method was investigated in the range of 0.05-0.8 % of test concentration. (r = 1) for Aripiprazole, 0.05-0.8 % (r = 1) for N-Oxide. Specificity of the method was established by determining the peak purity of the peaks of the drugs in a stress samples using PDA detector. Data suggests that peak purity of Aripiprazole in all degradation condition represents no co-elution of any degradation products. Placebo preparation was also analyzed for specificity. LOQ & LOD for Aripiprazole & N-Oxide impurity were found to be 0.0219, 0.0072 and 0.009380, 0.003094 respectively. HPLC method was developed for dissolution study of Aripiprazole in Orodispersible tablets. The separation was achieved on Inertsil ODS C18 (3V,150 X 4.6mm, 5μ) column and using mixture of acetonitrile, methanol and buffer (27.5: 27.5: 45) at pH 3.2 ± 0.05 using glacial ortho phosphoric acid as eluent, at a flow rate of 1.5 ml/min. Detection was carried out at 248 nm. The linearity of the proposed method was investigated in the range of 5-125 % of test concentration. (r = 1) for Aripiprazole. Placebo preparation was also analyzed for specificity. The method was found to be rugged and precise within the linearity range.