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Year 2022, Volume: 26 Issue: 6, 1703 - 1712, 28.06.2025

Hemlata Nimje Rajashree Chavan Smita Pawar Meenakshi Deodhar

https://doi.org/10.29228/jrp.261
Cited By: 1

Abstract

References

  • [1] Sweetman SC. Martindale, The Complete Drug Reference, thirty-sixth ed., Pharmaceutical Press, London, UK, 2009, pp. 1389.
  • [2] Samama MM. The mechanism of action of rivaroxaban – an oral, direct Factor Xa inhibitor – compared with other anticoagulants. Thromb Res. 2011;127(6):497-504. [CrossRef]
  • [3] Perzborn E, Roehrig S, Straub A, Kubitza D, Mueck W, Laux V. Rivaroxaban: a new oral factor Xa inhibitor, arteriosclerosis thrombosis and vascular biology. Arterioscler Thromb Vasc Biol. 2010;30(3):376-381. [CrossRef]
  • [4] Mani H, Lindhoff-Last E. New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness. Drug Des Devel Ther. 2014;8:789-798. [CrossRef]
  • [5] Maryadele JO, Patrica EH, Peter HD, Kristin JR. The Merck Index, An Encyclopedia of Chemicals, Drugs and Biologicals, fifteenth ed., The Royal Society of Chemistry, 2013, pp. 1533-1534.
  • [6] Bhavyasri K, Dhanalakshmi C, Sumakanth M. Development and validation of ultraviolet-visible spectrophotometric method for estimation of rivaroxaban in spiked human plasma. J Pharm Sci Res. 2020;12(9):1215-1219.
  • [7] Celebier M, Kaynak MS, Altınoz S, Sahin S. UV spectrophotometric method for determination of the dissolution profile of rivaroxaban. Dissolution Technol. 2014;56-59. [CrossRef]
  • [8] Shukla AH, Shah PJ, Dedhiya PP, Vyas BA, Shah SA. Development and validation of an HPTLC method for rivaroxaban in human plasma for a pharmacokinetic study. Indian J Pharm Sci. 2020;82(2):315-320. [CrossRef]
  • [9] Rajan N, Anver BK. A stability-indicating ultra-performance liquid chromatographic method for estimation of related substances and degradants in rivaroxaban active pharmaceutical ingredient. J Pharm Res. 2014;8(11):1719-1725.
  • [10] Çelebier M, Reçber T, Koçak E, Altınöz S. RP-HPLC method development and validation for estimation of rivaroxaban in pharmaceutical dosage forms. Braz J Pharm Sci. 2013;49(2):359-366. [CrossRef]
  • [11] Sahoo S, Mekap SK. Assay comparison of rivaroxaban by new HPLC method with an existing method in tablet dosage form. Pharma Biol Eval. 2017;4(3):180-182.
  • [12] Mohamed AA, Al-Ghobashy MA, Lotfy HM. Investigation of the profile and kinetics of degradation of rivaroxaban using HPLC, TLC-densitometry and LC/MS/MS: application to pre-formulation studies. Bull Fac Pharm Cairo Univ. 2015;53(1):53–61. [CrossRef]
  • [13] Arous B, Al-Mardini MA, Ghazal H, Al-Lahham F. Stability-indicating method for the determination of rivaroxaban and its degradation products using LC-MS and TLC. Res J Pharm Tech. 2018;11(1):212-220. [CrossRef]
  • [14] Reddy GS, Prasad RSLN, Reddy LSK. Development and validation of HPLC-MS/MS method for rivaroxaban quantitation in human plasma using solid phase extraction procedure. Oriental J Chem. 2016;32(2):1145-1154.
  • [15] Çelebier M, Reçber T, Koçak E, Altınöz S, Kır S. Determination of rivaroxaban in human plasma by solid-phase extraction – high performance liquid chromatography. J Chromatogr Sci. 2016;54(2):216–220. [CrossRef]
  • [16] Gouveia F, Bicker J, Santos J, Rocha M, Alves G, Falcão A. Development, validation and application of a new HPLC-DAD method for simultaneous quantification of apixaban, dabigatran, edoxaban and rivaroxaban in human plasma. J Pharm Biomed Anal. 2020;181:113109. [CrossRef]
  • [17] Arous B, Al-Mardini MA, Karabet F, Daghestani M, Al-Lahham F, Al-Askar A. Development and validation of a liquid chromatography method for the analysis of rivaroxaban and determination of its production related impurities. Pharm Chem J. 2018;52(5):483-490. [CrossRef]
  • [18] Seshamamba BSV, Satyanarayana PVV, Sekaran CB. Application of stability indicating HPLC method with UV detector to the analysis of rivaroxaban in bulk and tablet dosage form. Chem Sci Trans. 2014;3(4):1546-1554. [CrossRef]
  • [19] Souri E, Mottaghi S, Zargarpoor M, Ahmadkhaniha R, Jalalizadeh H. Development of a stability-indicating HPLC method and a dissolution test for rivaroxaban dosage forms. Acta Chromatogr. 2016;283(3):347–361. [CrossRef]
  • [20] Kasad PA, Muralikrishna KS. Base degradation study and method development of rivaroxaban by RP-HPLC in bulk. Asian J Pharm Tech. 2013;3(3):98-101.
  • [21] Wingert NR, dos Santos NO, Nunes MA, Gomes P, Müller EI, Flores EM, Steppe M. Characterization of three main degradation products from novel oral anticoagulant rivaroxaban under stress conditions by UPLC-Q-TOF-MS/MS. J Pharm Biomed Anal. 2016;123(10):10-15. [CrossRef]
  • [22] Ramisetti NR, Kuntamukkala R. Development and validation of a stability indicating LC-PDA-MS/MS method for separation, identification and characterization of process related and stress degradation products of rivaroxaban. RSC Adv. 2014;4(44):23155-23167. [CrossRef]
  • [23] Palandurkar K, Richie B, Sai HS, Boddu MH, Lakade S, Kandekar U, Waghmare P. Quality risk assessment and DoE–Practiced validated stability-indicating chromatographic method for quantification of rivaroxaban in bulk and tablet dosage form. Acta Chromatogr. 2022:1-11. [CrossRef]
  • [24] Srivastava A. Quantitative estimation of D-penicillamine in pure and pharmaceutical samples using inhibitory kinetic spectrophotometric method. Biointerface Res Appl Chem. 2021;11(4):11404-11417. [CrossRef]

Development and validation of stability-indicating RP-HPLC method for rivaroxaban in tablet dosage form

Year 2022, Volume: 26 Issue: 6, 1703 - 1712, 28.06.2025

Hemlata Nimje Rajashree Chavan Smita Pawar Meenakshi Deodhar

https://doi.org/10.29228/jrp.261
Cited By: 1

Abstract

The goal of this study was to create an RP-HPLC method for analysing the anticoagulant rivaroxaban (RIV) and estimating associated degradants in drug and tablet dosage forms that are accurate, sensitive and validated. The analysis was carried out on a Phenomenex Luna C18 column (4.6 x 250mm, 5µm particle size) at 40°C in isocratic mode with mobile phase water and acetonitrile (45:55 v/v) at a flow rate of 1.2 ml/min and a wavelength of 249 nm. This method was validated for linearity and range, accuracy, precision, LOD, LOQ and robustness according to ICH guidelines and the findings were satisfactory. The current study was carried out under various stress circumstances in order to determine the chemical structure of the primary degradation products generated when the drug was exposed to hydrolysis (basic, acidic, neutral), oxidation and photolytic conditions. Retention time (tR) was found to be 4.191±0.01 min. The three primary degradation products D1 (tR shown at 1.813 min), D2 (tR shown at 2.229 min), and D3 (tR shown at 1.850 min) developed during stress conditions in 0.1N NaOH, 0.1N HCl and 30% H2O2, respectively, as revealed by chromatogram and mass spectra. Under the ion spray voltage of 5500 V for positive mode, the molecular ion [M+1] m/z 436.3 of RIV was seen. The fragment ion peak was observed at m/z 415.5, 338.6, and 149.2. In basic, acidic and oxidative environments, RIV was found to be degraded. Quadrapole MS/MS was used to identify these contaminants in drugs and drug products.

Keywords

Rivaroxaban RP-HPLC tablets validation stability-indicating method

References

  • [1] Sweetman SC. Martindale, The Complete Drug Reference, thirty-sixth ed., Pharmaceutical Press, London, UK, 2009, pp. 1389.
  • [2] Samama MM. The mechanism of action of rivaroxaban – an oral, direct Factor Xa inhibitor – compared with other anticoagulants. Thromb Res. 2011;127(6):497-504. [CrossRef]
  • [3] Perzborn E, Roehrig S, Straub A, Kubitza D, Mueck W, Laux V. Rivaroxaban: a new oral factor Xa inhibitor, arteriosclerosis thrombosis and vascular biology. Arterioscler Thromb Vasc Biol. 2010;30(3):376-381. [CrossRef]
  • [4] Mani H, Lindhoff-Last E. New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness. Drug Des Devel Ther. 2014;8:789-798. [CrossRef]
  • [5] Maryadele JO, Patrica EH, Peter HD, Kristin JR. The Merck Index, An Encyclopedia of Chemicals, Drugs and Biologicals, fifteenth ed., The Royal Society of Chemistry, 2013, pp. 1533-1534.
  • [6] Bhavyasri K, Dhanalakshmi C, Sumakanth M. Development and validation of ultraviolet-visible spectrophotometric method for estimation of rivaroxaban in spiked human plasma. J Pharm Sci Res. 2020;12(9):1215-1219.
  • [7] Celebier M, Kaynak MS, Altınoz S, Sahin S. UV spectrophotometric method for determination of the dissolution profile of rivaroxaban. Dissolution Technol. 2014;56-59. [CrossRef]
  • [8] Shukla AH, Shah PJ, Dedhiya PP, Vyas BA, Shah SA. Development and validation of an HPTLC method for rivaroxaban in human plasma for a pharmacokinetic study. Indian J Pharm Sci. 2020;82(2):315-320. [CrossRef]
  • [9] Rajan N, Anver BK. A stability-indicating ultra-performance liquid chromatographic method for estimation of related substances and degradants in rivaroxaban active pharmaceutical ingredient. J Pharm Res. 2014;8(11):1719-1725.
  • [10] Çelebier M, Reçber T, Koçak E, Altınöz S. RP-HPLC method development and validation for estimation of rivaroxaban in pharmaceutical dosage forms. Braz J Pharm Sci. 2013;49(2):359-366. [CrossRef]
  • [11] Sahoo S, Mekap SK. Assay comparison of rivaroxaban by new HPLC method with an existing method in tablet dosage form. Pharma Biol Eval. 2017;4(3):180-182.
  • [12] Mohamed AA, Al-Ghobashy MA, Lotfy HM. Investigation of the profile and kinetics of degradation of rivaroxaban using HPLC, TLC-densitometry and LC/MS/MS: application to pre-formulation studies. Bull Fac Pharm Cairo Univ. 2015;53(1):53–61. [CrossRef]
  • [13] Arous B, Al-Mardini MA, Ghazal H, Al-Lahham F. Stability-indicating method for the determination of rivaroxaban and its degradation products using LC-MS and TLC. Res J Pharm Tech. 2018;11(1):212-220. [CrossRef]
  • [14] Reddy GS, Prasad RSLN, Reddy LSK. Development and validation of HPLC-MS/MS method for rivaroxaban quantitation in human plasma using solid phase extraction procedure. Oriental J Chem. 2016;32(2):1145-1154.
  • [15] Çelebier M, Reçber T, Koçak E, Altınöz S, Kır S. Determination of rivaroxaban in human plasma by solid-phase extraction – high performance liquid chromatography. J Chromatogr Sci. 2016;54(2):216–220. [CrossRef]
  • [16] Gouveia F, Bicker J, Santos J, Rocha M, Alves G, Falcão A. Development, validation and application of a new HPLC-DAD method for simultaneous quantification of apixaban, dabigatran, edoxaban and rivaroxaban in human plasma. J Pharm Biomed Anal. 2020;181:113109. [CrossRef]
  • [17] Arous B, Al-Mardini MA, Karabet F, Daghestani M, Al-Lahham F, Al-Askar A. Development and validation of a liquid chromatography method for the analysis of rivaroxaban and determination of its production related impurities. Pharm Chem J. 2018;52(5):483-490. [CrossRef]
  • [18] Seshamamba BSV, Satyanarayana PVV, Sekaran CB. Application of stability indicating HPLC method with UV detector to the analysis of rivaroxaban in bulk and tablet dosage form. Chem Sci Trans. 2014;3(4):1546-1554. [CrossRef]
  • [19] Souri E, Mottaghi S, Zargarpoor M, Ahmadkhaniha R, Jalalizadeh H. Development of a stability-indicating HPLC method and a dissolution test for rivaroxaban dosage forms. Acta Chromatogr. 2016;283(3):347–361. [CrossRef]
  • [20] Kasad PA, Muralikrishna KS. Base degradation study and method development of rivaroxaban by RP-HPLC in bulk. Asian J Pharm Tech. 2013;3(3):98-101.
  • [21] Wingert NR, dos Santos NO, Nunes MA, Gomes P, Müller EI, Flores EM, Steppe M. Characterization of three main degradation products from novel oral anticoagulant rivaroxaban under stress conditions by UPLC-Q-TOF-MS/MS. J Pharm Biomed Anal. 2016;123(10):10-15. [CrossRef]
  • [22] Ramisetti NR, Kuntamukkala R. Development and validation of a stability indicating LC-PDA-MS/MS method for separation, identification and characterization of process related and stress degradation products of rivaroxaban. RSC Adv. 2014;4(44):23155-23167. [CrossRef]
  • [23] Palandurkar K, Richie B, Sai HS, Boddu MH, Lakade S, Kandekar U, Waghmare P. Quality risk assessment and DoE–Practiced validated stability-indicating chromatographic method for quantification of rivaroxaban in bulk and tablet dosage form. Acta Chromatogr. 2022:1-11. [CrossRef]
  • [24] Srivastava A. Quantitative estimation of D-penicillamine in pure and pharmaceutical samples using inhibitory kinetic spectrophotometric method. Biointerface Res Appl Chem. 2021;11(4):11404-11417. [CrossRef]
There are 24 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Analytical Chemistry, Pharmaceutical Delivery Technologies
Journal Section Articles
Authors

Hemlata Nimje

Rajashree Chavan

Smita Pawar

Meenakshi Deodhar

Publication Date June 28, 2025
Published in Issue Year 2022 Volume: 26 Issue: 6

Cite

APA Nimje, H., Chavan, R., Pawar, S., Deodhar, M. (2025). Development and validation of stability-indicating RP-HPLC method for rivaroxaban in tablet dosage form. Journal of Research in Pharmacy, 26(6), 1703-1712. https://doi.org/10.29228/jrp.261
AMA Nimje H, Chavan R, Pawar S, Deodhar M. Development and validation of stability-indicating RP-HPLC method for rivaroxaban in tablet dosage form. J. Res. Pharm. June 2025;26(6):1703-1712. doi:10.29228/jrp.261
Chicago Nimje, Hemlata, Rajashree Chavan, Smita Pawar, and Meenakshi Deodhar. “Development and Validation of Stability-Indicating RP-HPLC Method for Rivaroxaban in Tablet Dosage Form”. Journal of Research in Pharmacy 26, no. 6 (June 2025): 1703-12. https://doi.org/10.29228/jrp.261.
EndNote Nimje H, Chavan R, Pawar S, Deodhar M (June 1, 2025) Development and validation of stability-indicating RP-HPLC method for rivaroxaban in tablet dosage form. Journal of Research in Pharmacy 26 6 1703–1712.
IEEE H. Nimje, R. Chavan, S. Pawar, and M. Deodhar, “Development and validation of stability-indicating RP-HPLC method for rivaroxaban in tablet dosage form”, J. Res. Pharm., vol. 26, no. 6, pp. 1703–1712, 2025, doi: 10.29228/jrp.261.
ISNAD Nimje, Hemlata et al. “Development and Validation of Stability-Indicating RP-HPLC Method for Rivaroxaban in Tablet Dosage Form”. Journal of Research in Pharmacy 26/6 (June 2025), 1703-1712. https://doi.org/10.29228/jrp.261.
JAMA Nimje H, Chavan R, Pawar S, Deodhar M. Development and validation of stability-indicating RP-HPLC method for rivaroxaban in tablet dosage form. J. Res. Pharm. 2025;26:1703–1712.
MLA Nimje, Hemlata et al. “Development and Validation of Stability-Indicating RP-HPLC Method for Rivaroxaban in Tablet Dosage Form”. Journal of Research in Pharmacy, vol. 26, no. 6, 2025, pp. 1703-12, doi:10.29228/jrp.261.
Vancouver Nimje H, Chavan R, Pawar S, Deodhar M. Development and validation of stability-indicating RP-HPLC method for rivaroxaban in tablet dosage form. J. Res. Pharm. 2025;26(6):1703-12.

Cited By

Quantitative determination of rivaroxaban in pharmaceutical formulations by ultra performance liquid chromatography
European Journal of Life Sciences
https://doi.org/10.55971/EJLS.1535613