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. 2020 Jan;34(1):e4719.
doi: 10.1002/bmc.4719. Epub 2019 Nov 19.

Stability-indicating RP-HPLC method development and validation for determination of nine impurities in apixaban tablet dosage forms. Robustness study by quality by design approach

Velusamy B Subramanian  1 , Naresh Kumar Katari  1   2 , Thirupathi Dongala  3 , Sreekantha B Jonnalagadda  2
Affiliations

Stability-indicating RP-HPLC method development and validation for determination of nine impurities in apixaban tablet dosage forms. Robustness study by quality by design approach

Velusamy B Subramanian et al. Biomed Chromatogr. 2020 Jan.

Abstract

A quality by design (QbD) based high-resolution HPLC method is described for determination of impurities in apixaban (APX) in the tablet dosage form. Employing a simple and stability-indicating HPLC method, nine known impurities were quantified with good peak resolution. Mobile phase A (MP-A) was prepared with buffer and acetonitrile 90:10 v/v, while mobile phase B (MP-B) contained water and acetonitrile 10:90 v/v. The gradient program was 0 min, MP-A 75%, B 25%; 20 min, MP-A 65%, B 35%; 30 min, MP-A 40%, B 60%; 40min, MP-A 40%, B 60%; 42 min, MP-A 75%, B 25%; and 50 min, MP-A 75%, B 25%. The chromatographic separation was achieved using a Zorbax RX C18 250 × 4.6 mm column, 5 μm (1.0 ml min-1 , 280 nm, 50 μl) and a column temperature of 40°C. Several separation studies were carried out using design of experiments to optimize the method. Validation results confirm the applicability of the developed method for quality analysis and stability studies of the regular product on the manufacturing stream.

Keywords: RP-HPLC; apixaban; impurities; method development; quality by design; validation.

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REFERENCES

    1. Agnelli, G., Buller, H. R., Cohen, A., Curto, M., Gallus, A. S., Johnson, M., … Weitz, J. E. (2013). Oral apixaban for the treatment of acute venous thromboembolism. New England Journal of Medicine, 369, 799-808. https://doi.org/10.1056/NEJMoa1302507
    1. Alexander, J. H., Lopes, R. D., James, S., Kilaru, R., He, Y., Mohan, P., … Huber, K. (2011). Apixaban with antiplatelet therapy after acute coronary syndrome. New England Journal of Medicine, 365, 699-708.
    1. Awotwe-Otoo, D., Agarabi, C., Faustino, P. J., Habib, M. J., Lee, S., Khan, M. A., & Shah, R. B. (2012). Application of quality by design elements for the development and optimization of an analytical method for protamine sulfate. Journal of Pharmaceutical and Biomedical Analysis, 62, 61-67. https://doi.org/10.1016/j.jpba.2012.01.002
    1. Baldelli, S., Cattaneo, D., Pignatelli, P., Perrone, V., Pastori, D., Radice, S., … Clementi, E. (2016). Validation of an LC-MS/MS method for the simultaneous quantification of dabigatran, rivaroxaban and apixaban in human plasma. Bioanalysis, 8, 275-283. https://doi.org/10.4155/bio.15.261
    1. Connolly, S. J., Eikelboom, J., Joyner, C., Diener, H. C., Hart, R., Golitsyn, S., … Talajic, M. (2011). Apixaban in patients with atrial fibrillation. New England Journal of Medicine, 364, 806-817.

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