Development and validation of a UPLC-MS method for determination of atazanavir sulfate by the “analytical quality by design” approach

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Abstract

A UPLC-MS method for the estimation of atazanavir sulfate was developed using the “analytical quality by design” approach. The critical chromatographic quality attributes identified were retention time, theoretical plates and peak tailing. The critical method parameters established were percent of organic modifier, flow rate and injection volume. Optimization performed using Box-Behnken Design (BBD) established 10 % organic modifier, 0.4 mL min−1 flow rate and 6-µL injection volume as the optimum method conditions. Atazanavir sulfate eluted at 5.19 min without any interference. Method validation followed international guidelines. The method has proven linearity in the range of 10–90 µg mL−1. Recovery was between 100.2–101.0 % and precision within the accepted limits (RSD 0.2–0.7 %). LOD and LOQ were 2.68 and 8.14 µg mL−1, resp. Stress testing stability studies showed atazanavir sulfate to degrade under acidic and basic conditions. The suggested technique is simple, rapid and sustainable. It is, therefore, suggested for routine analysis of atazanavir sulfate.

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  • 1. J. La Bonte J. Lebbos A. Raja and P. Kirkpatrick Infectious Diseases Nat. Rev. Drug Discov. 3 (2004) S26–S32; https://doi.org/10.1038/nrd1409

  • 2. B. Hughes Tapping into combination pills for HIV Nat. Rev. Drug Discov. 8 (2009) 439–440; https://doi.org/10.1038/nrd2917

  • 3. A. Raja J. Lebbos and P. Kirkpatrick Atazanavir sulphate Nat. Rev. Drug Discov. 2 (2003) 857–858; https://doi.org/10.1038/nrd1232

  • 4. K. Geetha Bhavani K. Bala Murali Krishna N. Srinivasu D. Ramachandran N. V. V. S. S Raman and B. Hari Babu Determination of genotoxic impurity in atazanavir sulphate drug substance by LC-MS J. Pharm. Biomed. Anal. 132 (2017) 156–158; https://doi.org/10.1016/j.jpba.2016.09.025

  • 5. K. Watanabe E. Varesio and G. Hopfgartner Parallel ultra high pressure liquid chromatography-mass spectrometry for the quantification of HIV protease inhibitors using dried spot sample collection format J. Chromatogr. B 965 (2014) 244–253; https://doi.org/10.1016/j.jchromb.2014.05.008

  • 6. S. Colombo N. Guignard C. Marzolini A. Telenti J. Biollaz and L. A. Decosterd Determination of the new HIV-protease inhibitor atazanavir by liquid chromatography after solid-phase extraction J. Chromatogr. B 810 (2004) 25–34; https://doi.org/10.1016/j.jchromb.2004.07.008

  • 7. A. Loregian S. Pagni E. Ballarin E. Sinigalia S. G. Parisi and G. Palù Simple determination of the HIV protease inhibitor atazanavir in human plasma by high-performance liquid chromatography with UV detection J. Pharm. Biomed. Anal. 42 (2006) 500–505; https://doi.org/10.1016/j.jpba.2006.04.031

  • 8. S. Dey S. S. Patro N. S. Babu P. N. Murthy and S. K. Panda Development and validation of a stability-indicating RP–HPLC method for estimation of atazanavir sulfate in bulk J. Pharm. Anal. 7 (2017) 134–140; https://doi.org/10.1016/j.jpha.2013.12.002

  • 9. C. H. Bhirud and S. N. Hiremath Stability indicating RP-HPLC method for the determination of atazanavir sulphate in bulk and dosage form Drug Invent. Today 5 (2013) 81–86; https://doi.org/10.1016/j.dit.2013.05.008

  • 10. L. Else V. Watson J. Tjia A. Hughes M. Siccardi S. Khoo and D. Back Validation of a rapid and sensitive high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) assay for the simultaneous determination of existing and new antiretroviral compounds J. Chromatogr. B 878 (2010) 1455–1465; https://doi.org/10.1016/j.jchromb.2010.03.036

  • 11. M. Mirochnick B. M. Best A. M. Stek E. V. Capparelli C. Hu S. K. Burchett S. S. Rossi E. Hawkins M. Basar E. Smith and J. S. Read Atazanavir pharmacokinetics with and without tenofovir during pregnancy JAIDS J. Acquir. Immune Defic. Syndr. 56 (2011) 412–419; https://doi.org/10.1097/QAI.0b013e31820fd093

  • 12. S. Goutelle T. Baudry M.-C. Gagnieu A. Boibieux J.-M. Livrozet D. Peyramond C. Chidiac M. Tod and T. Ferry (on behalf of the Lyon HIV Cohort Study Group) Pharmacokinetic-pharmaco-dynamic modeling of unboosted atazanavir in a cohort of stable HIV-infected patients Antimicrob. Agents Chemother. 57 (2013) 517–523; https://doi.org/10.1128/AAC.01822-12

  • 13. C. S. Venuto K. Mollan Q. Ma E. S. Daar P. E. Sax M. A. Fischl A. C. Collier K. Y. Smith C. Tierney and G. D. Morse (on behalf of AIDS Clinical Trial Group Study A5202 Team) Sex differences in atazanavir pharmacokinetics and associations with time to clinical events: AIDS Clinical Trials Group Study A5202 J. Antimicrob. Chemother. 69 (2014) 3300–3310; https://doi.org/10.1093/jac/dku303

  • 14. D. K. Lloyd and J. Bergum Application of quality by design (QbD) to the development and validation of analytical methods in: Specification of Drug Substances and Products - Development and Validation of Analytical Methods (C. M. Riley T. W. Rosanske and S. R. Rabel Riley Eds.) Elsevier Amsterdam 2014 pp. 29–72.

  • 15. B. Kelley M. Cromwell and J. Jerkins Integration of QbD risk assessment tools and overall risk management Biologicals 44 (2016) 341–351; https://doi.org/10.1016/j.biologicals.2016.06.001

  • 16. P. K. Sahu N. R. Ramisetti T. Cecchi S. Swain C. S. Patro and J. Panda An overview of experimental designs in HPLC method development and validation J. Pharm. Biomed. Anal. 147 (2018) 590–611; https://doi.org/10.1016/j.jpba.2017.05.006

  • 17. M. de Matas T. De Beer S. Folestad J. Ketolainen H. Lindén J. A. Lopes W. Oostra M. Weimer P. Öhrngren and J. Rantanen Strategic framework for education and training in Quality by Design (QbD) and process analytical technology (PAT) Eur. J. Pharm. Sci. 90 (2016) 2–7; https://doi.org/10.1016/j.ejps.2016.04.024

  • 18. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline Validation of Analytical Procedures: Pharmaceutical Development Q8 (R2) Current Step 4 version August 2009; http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf; last access date March 10 2018.

  • 19. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline Validation of Analytical Procedures: Quality Risk Management Q9 Current Step 4 version November 2005; http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q9/Step4/Q9_Guideline.pdf last access date March 10 2018.

  • 20. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline Validation of Analytical Procedures: Pharmaceutical Quality System Q10 Current Step 4 version June 2008; http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q10/Step4/Q10_Guideline.pdf last access date March 10 2018.

  • 21. J. Kochling W. Wu Y. Hua Q. Guan and J. Castaneda-Merced A platform analytical quality by design (AQbD) approach for multiple UHPLC-UV and UHPLC–MS methods development for protein analysis J. Pharm. Biomed. Anal. 125 (2016) 130–139; https://doi.org/10.1016/j.jpba.2016.03.031

  • 22. G. L. Reid J. Morgado K. Barnett B. Harrington J. Wang J. Harwood and D. Fortin Analytical Quality by Design (AQbD) in pharmaceutical development Am. Pharm. Rev. 16 (2013); https://www.americanpharmaceuticalreview.com/Featured-Articles/144191-Analytical-Quality-by-Design-AQbD-in-Pharmaceutical-Development/; last access date December 26 2018.

  • 23. P. S. Sandhu S. Beg R. Kumar O. P. Katare and B. Singh Analytical QbD-based systematic bio-analytical HPLC method development for estimation of quercetin dihydrate J. Liq. Chromatogr. Relat. Technol. 40 (2017) 506–516; https://doi.org/10.1080/10826076.2017.1329744

  • 24. A. Dispas H. T. Avohou P. Lebrun P. Hubert and C. Hubert ‘Quality by Design’ approach for the analysis of impurities in pharmaceutical drug products and drug substances Trends Anal. Chem. 101 (2017) 24–33; https://doi.org/10.1016/j.trac.2017.10.028

  • 25. T. Schofield D. Robbins and G. Miró-Quesada Critical Quality Attributes Specifications and Control Strategy in Quality by Design for Biopharmaceutical Drug Product Development (Eds. F. Jameel S. Hershenson M. A. Khan and S. Martin-Moe) /Advances in the Pharmaceutical Sciences Series AAPS Vol. 18 (Eds. D. J. A. Crommelin and R. A. Lipper)/Springer New York pp. 511–535.

  • 26. U. S. Food and Drug Administration (FDA) Center for drug evaluation and research (CDER) Reviewer Guidance-Validation of Chromatographic Methods November 1994; https://www.fda.gov/downloads/Drugs/Guidances/UCM134409.pdf; last access date December 26 2018

  • 27. What is peak tailing? Chromatogr. Today August 8 2014; https://www.chromatographytoday.com/news/autosamplers/36/breaking-news/what-is-peak-tailing/31253; last access date December 26 2018.

  • 28. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline Validation of Analytical Procedures: Text and Methodology Q2 (R1) Current Step 4 version November 2005; https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf; last access date March 10 2018.

  • 29. T. Sharma R. K. Khurana A. Jain O. P. Katare and B. Singh Development of a validated liquid chromatographic method for quantification of sorafenib tosylate in the presence of stress-induced degradation products and in biological matrix employing analytical quality by design approach Biomed. Chromatogr. 32 (2018) e4169; https://doi.org/10.1002/bmc.4169

  • 30. N. K. Garg G. Sharma B. Singh P. Nirbhavane and O. P. Katare Quality by Design (QbD)-based development and optimization of a simple robust RP-HPLC method for the estimation of methotrexate J. Liq. Chromatogr. Relat. Technol. 38 (2015) 1629–1637; https://doi.org/10.1080/10826076.2015.1087409

  • 31. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline Validation of Analytical Procedures: Stability Testing of New Drug Substances and Products Q1A(R2) Current Step 4 version February 2003; http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1A_R2/Step4/Q1A_R2__Guideline.pdf; last access date March 10 2018.

  • 32. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline Validation of Analytical Procedures: Stability Testing: Photostability Testing of New Drug Substances and Products Q1B Current Step 4 version November 1996; http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1B/Step4/Q1B_Guideline.pdf; last access date March 10 2018.

  • 33. L. Zhang and S. Mao Application of quality by design in the current drug development Asian J. Pharm. Sci. 12 (2017) 1–8; https://doi.org/10.1016/j.ajps.2016.07.006

  • 34. A. Loregian S. Pagni E. Ballarin E. Sinigalia S. G. Parisi and G. Palù Simple determination of the HIV protease inhibitor atazanavir in human plasma by high-performance liquid chromatography with UV detection J. Pharm. Biomed. Anal. 42 (2006) 500–505; https://doi.org/10.1016/j.jpba.2006.04.031

  • 35. S. R. Chitturi Y. S. Somannavar B. G. Peruri S. Nallapati H. K. Sharma S. R. Budidet V. K. Handa and H. B. Vurimindi Gradient RP-HPLC method for the determination of potential impurities in atazanavir sulfate J. Pharm. Biomed. Anal. 55 (2011) 31–47; https://doi.org/10.1016/j.jpba.2011.01.002

  • 36. M. K. V. V. N. Mantripragada S. V. Rao V. V. S. Nutulapati and B. P. V. Mantena Simultaneous determination of impurities of atazanavir and ritonavir in tablet dosage form by using reversed-phase ultra performance liquid chromatographic method J. Chromatogr. Sci. 56 (2018) 270–284; https://doi.org/10.1093/chromsci/bmx110

  • 37. N. Phung K. Kuncze H. Okochi A. Louie L. Z. Benet I. Ofokotun D. W. Haas J. S. Currier T. D. Chawana A. N. Sheth P. Bacchetti M. Gandhi and H. Horng Development and validation of an assay to analyze atazanavir in human hair via liquid chromatography/tandem mass spectrometry Rapid Commun. Mass Spectrom. 32 (2018) 431–441; https://doi.org/10.1002/rcm.8058

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