ULTRA HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF GENOTOXIC IMPURITIES IN FEBUXOSTAT DRUG SUBSTANCE AND PRODUCTS

  • Balaji N St. Peter’s University, Avadi, Chennai
  • Sayeeda Sultana

Abstract

Objective: An efficient ultra-high performance liquid chromatographic (UHPLC or Infinity LC 1290) method has been developed and validated for the quantification of possible carcinogenic or genotoxic impurities in febuxostat drug substances and drug products at 18 µg/ml level.

Methods: This method includes the conclusion of four potential genotoxic impurities in febuxostat. The mobile phase is trifluoroacetic acid, acetonitrile, and water with linear gradient elution. The UHPLC column used for the analysis was zorbax RRHD eclipse plus C18 with a length of100 mm, internal diameter of 2.1 mm, and particle size of 1.8 µ.

Results: The limit of detection and limit of quantitation of the impurities are <0.1 (0.00001%) and 0.3 µg/ml (0.00003%) with respect to febuxostat test concentration of 1000 µg/ml, respectively. This method has been validated as per ICH guidelines Q2 (R1).

Conclusion: A rapid, cost-effective infinity LC method was wonderfully established for quantitative analysis of possible genotoxic impurities of febuxostat drug substance and drug products.

Keywords: Febuxostat, Genotoxic impurities, Ultra-high performance liquid chromatograph, Infinity-LC 1290, Validation

Author Biography

Balaji N, St. Peter’s University, Avadi, Chennai
Department of Chemistry, St. Peter’s University, Avadi, Chennai- 600 054, Tamil Nadu, India

References

1. Febuxostat for the Management of Hyperuricemia in People with Gout (TA164). Ch. 4. Consideration of the Evidence. Available from: https:// www.nice.org.uk/guidance/ta164/chapter/4-consideration-of-the- evidence.
2. ULORIC (Febuxostat) Tablet for Oral Use Initial U.S. Approval;2009. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf.
3. Chandu BR, Kanala K, Hwisa NT, Katakam P, Khagga M. Bioequivalance and pharmacokinetic study of febuxostat in human plasma by using LC-MS/MS with liquid liquid extraction method. Springerplus 2013;2(1):194.
4. Shi Z, Liu J, Hu XJ, Tu JZ. Development of a simple LC-MS/MS method for the determination of febuxostat in human plasma and its application to a bioequivalence study. Pharmazie 2013;68(6):396-400.
5. Vaka VR, Inamadugu JK, Pilli NR, Ramesh M, Katreddi HR. A sensitive LC-MS/MS method for the quantification of febuxostat in human plasma and its pharmacokinetic application. Biomed Chromatogr 2013;27(11):1406-12.
6. Lukram O, Parmar S, Hande A. Determination of febuxostat in human plasma using ultra-performance liquid chromatography tandem mass spectrometry. Drug Test Anal 2013;5(6):492-9.
7. Younes KM, El-Kady EF, Elzanfaly ES. Determination of febuxostat in human plasma using RP-LC-UV method. J Chromatogr Sci 2016;54(6):1022-7.
8. Rao KN, Ganapaty S, Rao LA. Development and validation of RP- HPLC method for estimation of febuxostat in bulk and tablet dosage form. Int J Res Pharm Chem 2012;2(4):1104-8.
9. Ravisankar P, Rani AK, RamanaVK, Gowthami S. Development and validation of rapid RP - HPLC method for the determination of febuxostat (a non-purine selective xanthine-oxidase/xanthine- dehydrogenase inhibitor) in bulk and pharmaceutical dosage form. World J Pharm Pharm Sci 2015;4(9):1046-61.
10. Mukthinuthalapati MA, Bandaru SP, Bukkapatnam V, Mohapatro C. Development and validation of a stability-indicating RP-HPLC method for the determination of febuxostat (a xanthine oxidase inhibitor). J Chromatogr Sci 2013;51(10):931-8.
11. Molleti S, Rao V, Jayaveera KN. A stability indicating RP-UPLC method for estimation of febuxostat and its impurities in bulk drugs and pharmaceutical dosage forms. Am J Pharm Tech Res 2013;3(2):405-22.
12. Sahu K, Shaharyar M, Siddiqui SA. Establishment of the inherent stability of febuxostat and development of a validated stability- indicating method by UPLC according to ICH requirement. Med Chem Res 2013;22(4):1641-7.
13. Musirike MR, Reddy HK, Mallu UR. Development and validation of reverse phase-ultra performance liquid chromatographic method for estimation of related substances in febuxostat drug substance. Pharm Anal Acta 2015;6(10):1-6.
14. Zhang T, Sun Y, Zhang P, Gao J, Wang S, He Z. Ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of febuxostat in dog plasma and its application to a pharmacokinetic study. Biomed Chromatogr 2013;27(2):137-41.
15. Pharmaceutical Development Q8(R2). Available from:
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf.
16. Vogt FG, Kord AS. Development of quality-by-design analytical methods. J Pharm Sci 2011;100(3):797-812.
17. Reid GL, Morgado J, Barnett K, Harrington B, Wang J, Harwood J, et al. Analytical quality by design (AQbD) in pharmaceutical development. Am Pharm 2013;16:49-59.
18. Debrus B, Guillarme D, Rudaz D. Improved quality-by-design compliant methodology for method development in reverse-phase liquid chromatography. J Pharm Biomed Anal 2013;84:215-23.
19. Validation of Analytical Procedures: Text and Methodology Q2(R1). Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_ Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1 Guideline.pdf.
20. Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings Safety and Health, DHHS (NIOSH). Available from: https://www.cdc.gov/niosh/docs/2004-165/.
21. OECD Quantitative Structure-Activity Relationships Project [(Q) SARs]. Available from: http://www.oecd.org/chemicalsafety/testing/ oecdquantitativestructure-activityrelationshipsprojectqsars.htm.
22. Roy K, Kar S, Das RN. Understanding the Basics of QSAR for Applications in Pharmaceutical Sciences and Risk Assessment. New York: Academic Press, Elsevier; 2015.
23. Stability Testing: Photostability Testing of New Drug Substances and Products Q1B. Available from: http://www.ich.org/fileadmin/ Public_Web_Site/ICH_Products/Guidelines/Quality/Q1B/Step4/Q1B_ Guideline.pdf.
24. Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk M7. Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/ Guidelines/Multidisciplinary/M7/M7_Step_4.pdf.
25. Available from: http://www.drugbank.ca/drugs/DB04854.
26. Ravi P, Shanmugam V, Lahoti AM, Deepthi PS, Innareddy V, Rao S,
et al. Investigation of various impurities in febuxostat. Pharm Technol 2014;38(9):1-6.
27. Balaji N, Sayeeda S. Trace level determination and quantification of potential genotoxic impurities in dasatinib drug substance by UHPLC/ infinity LC. Int J Pharm Pharm Sci 2016;8(10):209-16.
28. Mercy R, Suja R, Caroling G, Tiwari S. In vitro evaluation of antioxidant, antimicrobial, anticancer activities and characterization of Brassica oleracea. Var. Bortrytis. L synthesized silver nanoparticles. Int J Pharm Pharm Sci 2013;5(4):239-51.
29. Manisha B, Priyanka P. Development and evaluation of paclitaxel loaded nanoparticles using 24 factorial design. Int J Curr Pharm Res 2015;7(2):64-72.
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How to Cite
N, B., and S. Sultana. “ULTRA HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF GENOTOXIC IMPURITIES IN FEBUXOSTAT DRUG SUBSTANCE AND PRODUCTS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 1, Jan. 2017, pp. 324-30, doi:10.22159/ajpcr.2017.v10i1.15381.
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