Development of a validated RP-HPLC assay method for quantitative separation of Teriflunomide and its process-related impurities in bulk drugs

Bhagavan Rajesh Babu Koppisetty; Rajendra Prasad Yejella; A. Krishna Manjari Pawar; Srinivasa Rao Yarraguntla; Varaprasada Rao Kollabathula; Vasudha Dadi; Challa Gangu Naidu

doi:10.7324/JAPS.2023.129159

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Abstract

The organic, inorganic, and residual solvent impurity sources in pharmacological compounds have been divided into categories by the International Council for Harmonization. The pharmaceutical sector faces a regulatory hurdle since the organic contaminants could be genotoxins. The detection and method development also a validation of organic contaminants produced during the chromatographic separation of a teriflunomide is the main goal of this work. The impurity profile research was carried out using a diode array detector and reverse phase-high performance liquid chromatography. At a column temperature of 25°C, the C18 YMC-Pack ODS column was successfully achieved through gradient separation. As the mobile phase, acetonitrile and 0.015 M potassium dihydrogen phosphate with a pH of 3.5 were employed. A 210 nm detector wavelength and 1.0 ml/minute flow rate were adopted. Six process-related impurities were successfully separated using the validated analytical method, with resolution and retention times under 35 minutes. Teriflunomide, Teriflunomide stage-1, and Impurity-D have established analytical techniques with ranges of 0.066–3.262, 0.035–1.880, and 0.025–1.255 μg/ml, respectively. Teriflunomide, Teriflunomide stage-1, and impurity-D have respective limits of detection and limit of quantification values of 0.0037 and 0.0096, 0.0016 and 0.0051, and 0.0011 and 0.0033 μg/ml. The confirmed analytical approach can effectively identify any manufacturing process impurities.

Citation:

Koppisetty BRB, Yejella RP, Pawar AKM, Yarraguntla SR, Kollabathula VR, Dadi V, Naidu CG. Development of a validated RP-HPLC assay method for quantitative separation of Teriflunomide and its process related impurities in bulk drugs. J Appl Pharm Sci, 2023; 13(Suppl 1):028–033. https://doi.org/10.7324/JAPS.2023.129159

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

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https://pubchem.ncbi.nlm.nih.gov/compound/4-_ Trifluoromethyl_aniline (Accessed 17 December 2022)

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Koppisetty B R B [PubMed] [Google Scholar ]

Yejella R P [PubMed] [Google Scholar ]

Pawar A K M [PubMed] [Google Scholar ]

Yarraguntla S R [PubMed] [Google Scholar ]

Kollabathula V R [PubMed] [Google Scholar ]

Dadi V [PubMed] [Google Scholar ]

Naidu C G [PubMed] [Google Scholar ]

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European Medicines Agency. European Public Assessment Report. AUBAGIO (International non-proprietary name: Teriflunomide), Procedure No. EMEA/H/C/002514/0000. European Medicines Agency, EMA/529295/2013, 2013.

ICH. Validation of analytical procedures, International Conference on Harmonization, IFPMA, Geneva, Switzerland, 1994.

Lakshmi GT, Srinivasa RY, Varaprasadrao K, Hemant KT. RP-HPLC method for estimation of atomoxetine hydrochloride in bulk and pharmaceutical dosage form. Res J Pharm Biol Chem Sci, 2015; 2:1208-14.

Nukendra PN, Venkatanadh R, Srinivasu N. Quality-by-design-based development and validation of a stability-indicating UPLC method for quantification of teriflunomide in the presence of degradation products and its application to in-vitro dissolution. J Liq Chromatogr Relat Technol, 2017; 40(10):517-27. https://doi.org/10.1080/10826076.2017.1330211

Pandey S, Mahtab A, Singh A, Ahmad FJ, Aqil M, Talegaonkar S. Development and validation of stability indicating reversed-phase liquid chromatographic method for simultaneous quantification of methotrexate and teriflunomide in nanoparticles and marketed formulation. Biomed Chromatogr, 2018; 32(12):e4372. https://doi.org/10.1002/bmc.4372

Parekh JM, Vaghela RN, Sutariya DK, Sanyal M, Yadav M, Shrivastav PS. Chromatographic separation and sensitive determination of teriflunomide, an active metabolite of leflunomide in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci, 2010; 878(24):2217-5. https://doi.org/10.1016/j.jchromb.2010.06.028

Rakhila H, Rozek T, Hopkins A, Proudman S, Cleland L, James M, Wiese M. Quantitation of total and free teriflunomide (A77 1726) in human plasma by LC-MS/MS. J Pharm Biomed Anal, 2011; 55(2):325-31. https://doi.org/10.1016/j.jpba.2011.01.034

Rule GS, Rockwood AL, Johnson-Davis KL. LC-MS/MS Method for the quantification of the leflunomide metabolite, teriflunomide, in human serum/plasma. Methods Mol Biol, 2019; 1872:75-83. https://doi.org/10.1007/978-1-4939-8823-5_8

Srinivasa YR, Gandi P, Varaprasadrao K, Hemant KT. Development and validation of visible spectrophotometric method for the estimation of zaltoprofen in tablet dosage form. Der Pharm Lett, 2015; 7(1):196-201.

Suneetha A, Raja RK. Comparison of LC-UV and LC-MS methods for simultaneous determination of teriflunomide, dimethyl fumarate and fampridine in human plasma: application to rat pharmacokinetic study. Biomed Chromatogr, 2016; 30(9):1371-7. https://doi.org/10.1002/bmc.3694

Vidyadhara, Suryadevara, Srinivasa RY, Ramu A, Sasidhar RL, Ramya JA. Method development and validation for the simultaneous estimation of cinitapride and pantoprazole in solid dosage forms by RP-HPLC. Orient J Chem, 2013; 29(3):1213. https://doi.org/10.13005/ojc/290355

https://pubchem.ncbi.nlm.nih.gov/compound/Teriflunomide (Accessed 17 December 2022).

h t t p s : / / p u b c h e m . n c b i . n l m . n i h . g o v / c o m p o u n d / 5 - Methylisoxazole-4-carboxylic-acid (Accessed 17 December 2022).

https://pubchem.ncbi.nlm.nih.gov/compound/21912858 (Accessed 17 December 2022).

https://pubchem.ncbi.nlm.nih.gov/compound/5-Methyl-N-_4- methylphenyl_isoxazole-4-carboxamide (Accessed 17 December 2022).

https://pubchem.ncbi.nlm.nih.gov/compound/4-_ Trifluoromethyl_aniline (Accessed 17 December 2022)