AJAC  Vol.5 No.17 , December 2014
Development and Validation of a Stability-Indicating RP-HPLC Method for Determination of Darifenacin Hydrobromide in Bulk Drugs
Abstract: An isocratic stability-indicating reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for determination of process related impurities and assay of darifenacin hydrobromide (DRF) in bulk drugs. DRF was subjected to various stress conditions such as hydrolysis (acid, base, and neutral), oxidation, photolysis and thermal degradation as per International Conference on Harmonization (ICH Q1A(R2) and Q1B) prescribed conditions to investigate the stability-indicating ability of the method. Significant degradation was observed during acidic hydrolysis and oxidative stress conditions. The chromatographic separation was accomplished on a Prodigy C8 column (250 × 4.6 mm, 5 μm) with mobile phase consisting of 0.05 M ammonium acetate (pH adjusted to 7.2 by using ammonia solution) and methanol (36% acetonitrile) in 35:65 v/v ratio in an isocratic elution mode at a flow rate of 1.0 mL/min at 25°C. Detection of analytes was carried out using photo diode array detector at a wavelength of 215 nm. The developed LC method was validated with respect to accuracy, linearity, precision, limits of detection and quantitation and robustness as per ICH guidelines.
Cite this paper: Nazeerunnisa, M. , Garikapati, L. and Bethanabhatla, S. (2014) Development and Validation of a Stability-Indicating RP-HPLC Method for Determination of Darifenacin Hydrobromide in Bulk Drugs. American Journal of Analytical Chemistry, 5, 1239-1248. doi: 10.4236/ajac.2014.517130.

[1]   Hashim, H. and Abrams, P. (2005) Treatment of Overactive Bladder Syndrome and Detrusor over Activity. Reviews in Gynaecological Practice, 5, 243-250.

[2]   Haab, F., Stewart, L. and Dwyer, P. (2004) Darifenacin an M3 Selective Receptor Antagonist, Is an Effective and Well-Tolerated Once-Daily Treatment for Overactive Bladder. European Urology, 45, 420-429.

[3]   Thomas, S., Paul, S.K., Shandilya, S., Agarwal, A., Saxena, N., Awasthi, A.K., Matta, H., Vir, D. and Mathel, C.S. (2012) Identification and Structural Elucidation of Two Process Impurities and Stress Degradants in Darifenacin Hydrobromide Active Pharmaceutical Ingredient by LC-ESI/MSn. Analyst, 137, 3571-3582.

[4]   Murthya, M.V., Krishnaiah, Ch., Srinivas, K., Rao, K.S., Kumar, N.R. and Mukkanti, K. (2013) Development and Validation Of RP-UPLC Method for the Determination of Darifenacin Hydrobromide, Its Related Compounds and Its Degradation Products Using Design of Experiments. Journal of Pharmaceutical and Biomedical Analysis, 72, 40-50.

[5]   Meneghini, L.Z., Junqueira, C., Andrade, A.S., Salazar, F.R., Codevilla, C.F., Froehlich, P.E. and Bergold, A.M. (2011) Chemometric Evaluation of Darifenacin Hydrobromide Using a Stability-Indicating Reversed-Phase LC Method. Journal of Liquid Chromatography & Related Technologies, 34, 2169-2184.

[6]   Murthy, M.V., Ragavacharyulu, K.S.V., Krishnaiah, C., Srinivas, K., Mukkanti, K. and Kumar, N.R. (2009) A Stereo-selective, Stability-Indicating Validated LC-Assay Method for the Separation and Quantification of Darifenacin and Its Enantiomer. Analytical Chemistry: An Indian Journal, 8, 491-493.

[7]   Radhakrishnanand, P., Rao, D.V.S. and Himabindu, V. (2008) A Validated LC Method for Determination of the Enantiomeric Purity of Darifenacin in Bulk Drug and Extended Release Tablets. Chromatographia, 68, 1059-1062.

[8]   Srinivas, K., Reddy, S.R., Reddy, G.M., Dubey, P.K., Chakravarthy, A.K. and Reddy, P.P. (2009) Synthesis and Characterization of Novel and Potential Impurities of Darifenacin, a Potent Muscarinic M3 Receptor Antagonist. Rasayan Journal of Chemistry, 2, 151-155.

[9]   Kaye, B., Herron, W.J., Macrae, P.V., Robinson, S., Stopher, D.A., Venn, R.F. and Wild, W. (1996) Rapid, Solid Phase Extraction Technique for the High-Throughput Assay of Darifenacin in Human Plasma. Analytical Chemistry, 68, 1658-1660.

[10]   ICH Q2(R1) (2005) International Conference on Harmonization, Validation of Analytical Procedures: Test and Methodology.

[11]   ICH Q1A (R2) (2003) International Conference on Harmonization, Stability Testing of New Drug Substance and Products.