Author(s):
Upama Surendra Singh, Navin Sainy
Email(s):
upama15190@gmail.com
DOI:
10.52711/0974-360X.2025.00873 
Address:
Upama Surendra Singh1*, Navin Sainy2
1Research Scholar, Department of Pharmacy, Oriental University Indore, Madhya Pradesh, India.
2Associate Professor, Department of Pharmacy, Oriental University Indore, Madhya Pradesh, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 12,
Year - 2025
ABSTRACT:
The rising application of cobicistat as a pharmacokinetic booster in antiretroviral therapy requires accurate and efficient biophysical and chiral analyses of impurities and enantiomers. This work describes a new analytical technique that has been created and tested for the identification of impurities and determination of chiral purity of cobicistat. While employing advanced chromatographic methods, it proves that sensitivity as well as specificity is very high in terms of detecting and measuring the level of impurities. In addition, to have the pure form of the drug, chiral separation was also carried out to prevent the formation of racemic mixture. Some of the validated parameters for the method were linearity, accuracy, precision, limit of detection, limit of quantification and robustness. The obtained results proved that the developed method is reliable, sensitive, accurate and suitable for routine quality control of cobicistat and its efficacy and safety in the clinical practices.
Cite this article:
Upama Surendra Singh, Navin Sainy. Advanced Analytical Method Development and Validation for Comprehensive Impurity and Chiral Impurity Analysis of Cobicistat in Anti-Retroviral Regimens. Research Journal Pharmacy and Technology. 2025;18(12):6042-8. doi: 10.52711/0974-360X.2025.00873
Cite(Electronic):
Upama Surendra Singh, Navin Sainy. Advanced Analytical Method Development and Validation for Comprehensive Impurity and Chiral Impurity Analysis of Cobicistat in Anti-Retroviral Regimens. Research Journal Pharmacy and Technology. 2025;18(12):6042-8. doi: 10.52711/0974-360X.2025.00873 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2025-18-12-63
REFERENCES:
1. Jain P, Thota A, Saini PK, Raghuvanshi RS. Comprehensive review on different analytical techniques for HIV-1 integrase inhibitors: Raltegravir, Dolutegravir, Elvitegravir, and Bictegravir. Crit Rev Anal Chem. 2022; 54(2): 401-15. doi:10.1080/10408347.2022.2080493.
2. Muccini C, Castagna A. A four-drug combination oral tablet of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide for the treatment of HIV-1 infection in adults. Expert Rev Anti-Infect Ther. 2023; 21(11): 1167-76. doi:10.1080/14787210.2023.2268281.
3. Cattaneo D, Pagano S, Antinori S, Micheli V, Gori A, Gervasoni C. Effect of doravirine on dolutegravir trough concentrations in people with HIV switched from darunavir/cobicistat. J Antimicrob Chemother. 2023; 78(6): 1547-8. doi:10.1093/jac/dkad100.
4. Marin RC, Behl T, Negrut N, Bungau S. Management of antiretroviral therapy with boosted protease inhibitors Darunavir/Ritonavir or Darunavir/Cobicistat. Biomedicines. 2021; 9(3): 313. doi:10.3390/biomedicines9030313.
5. Lamichhane S, Das B, Adhikari RP, Jeyaprakash MR. Overview of forced degradation analysis for FDA-approved antiretroviral agents: A review. J Young Pharm. 2022; 14(3): 273-82. doi:10.5530/jyp.2022.14.55.
6. Ganji S, Satyavati D. Development and validation of RP-HPLC method for the analysis of Cobicistat and related impurities in bulk and pharmaceutical dosage forms. Asian J Pharm Anal. 2015; 5(1): 1-8. doi:10.5958/2231-5675.2015.00001.0.
7. Madhavi S, Rani AP. Development and validation of a bioanalytical method for the determination of Cobicistat from human plasma. Asian J Pharm Anal. 2016; 6(4): 216-26. doi:10.5958/2231-5675.2016.00033.8.
8. Swetha V, Prasad SV, Rani YA. Analytical method development and validation for simultaneous estimation of Cobicistat and Elvitegravir using RP-HPLC in pure and pharmaceutical dosage forms. Asian J Pharm Anal. 2017; 7(3): 151-8. doi:10.5958/2231-5675.2017.00024.2.
9. Swetha E, Prasad SVU, Rani YA. Analytical method development and validation for simultaneous estimation of Cobicistat and Elvitegravir using RP-HPLC in pure and pharmaceutical dosage forms. Asian J Pharm Anal. 2017; 7(3): 151-8. doi:10.5958/2231-5675.2017.00024.2.
10. Kumari KP, Sankar DG. Stability-indicating UPLC method for simultaneous estimation of Emtricitabine, Bictegravir, and Tenofovir Alafenamide. Indian Drugs. 2020; 57(1). doi:10.53879/id.57.01.11717.
11. Madhavi S, Rani AP. Development and validation of RP-UPLC method for simultaneous estimation of Cobicistat and Darunavir. Res J Pharm Technol. 2017; 10(12): 4343-9. doi:10.5958/0974-360X.2017.00796.X.
12. Padmini MV, Sankar DG. Stability-indicating RP-UPLC method for simultaneous estimation of Atazanavir and Cobicistat in bulk and tablet dosage forms. Res J Pharm Technol. 2021; 14(3): 1412-6. doi:10.5958/0974-360X.2021.00252.3.
13. Jain P, Thota A, Saini PK, Raghuvanshi RS. Comprehensive review on different analytical techniques for HIV-1 integrase inhibitors: Raltegravir, Dolutegravir, Elvitegravir, and Bictegravir. Crit Rev Anal Chem. 2022; 54(2): 401-15. doi:10.1080/10408347.2022.2080493.
14. Dadi V, Sowjanya G. Development and validation of UPLC method for simultaneous estimation of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide in bulk drug and pharmaceutical dosage form. Res J Pharm Technol. 2023; 16(5): 2336-42. doi:10.52711/0974-360X.2023.00384.
15. Ashwini SJ, Narenderan ST, Meyyanathan SN, Babu B, Gowramma B. A validated chiral HPLC method for the enantiomeric separation of Mefloquine. Res J Pharm Technol. 2019; 12(5): 2304-8. doi:10.5958/0974-360X.2019.00384.6.
16. Sevrioukova IF. Interaction of CYP3A4 with the inhibitor Cobicistat: Structural and mechanistic insights and comparison with Ritonavir. Arch Biochem Biophys. 2024; 758: 110071. doi:10.1016/j.abb.2024.110071.
17. Saminathan J, Vetrichelvan T. Development and validation of HPTLC method for simultaneous estimation of Emtricitabine, Rilpivirine, and Tenofovir Disoproxil Fumarate in combined dosage form. Bangladesh Pharm J. 2016; 19(1): 114-21. doi:10.3329/bpj.v19i1.29247.
18. Younes OM, Ali FA, Al Assaf Z. Separation of Carvedilol enantiomers using HPLC by two different methods: Mobile phase chiral additive and chiral stationary phase. Res J Pharm Technol. 2020; 13(4): 1679-83. doi:10.5958/0974-360X.2020.00304.2.
19. Rajana N, Pallavi V, Madhavan P, Mohan HR, Babu JM, Basavaiah K. Absolute configuration of Boceprevir chiral fragment-b by chiral chromatographic, spectroscopic, thermal, and crystallization techniques. Asian J Res Chem. 2018; 11(3): 671-80. doi:10.5958/0974-4150.2018.00120.7.
20. Jabeen N, Haque MA. A review on bioanalytical method development and validation for estimation of drugs using hyphenated techniques and its applications in routine analysis. Arch Curr Res Int. 2023; 23(2): 18-35. doi:10.9734/acri/2023/v23i2556.
21. Patel K, Shah U, Joshi H, Patel JK, Patel TB. Development, validation, and forced degradation study of Emtricitabine and Tenofovir Alafenamide in pharmaceutical dosage form using RP-HPLC. J Pharm Res Int. 2021; 33(43A): 37-46. doi:10.9734/JPRI/2021/v33i43A32462.
22. Holm R, Elder DP. Analytical advances in pharmaceutical impurity profiling. European Journal of Pharmaceutical Sciences. 2016; 87: 118-35. doi.org/10.1016/j.ejps.2015.12.007
23. Venkatesan P, Valliappan K. Impurity profiling: theory and practice. Journal of Pharmaceutical Sciences and Research. 2014; 6(7): 254.
24. Dighe V, Pawaskar P, Adhyapak S, Shambhu N, Mestry D. Development of reverse phase chiral liquid chromatographic method for determination of sertraline 1R4R cis enantiomer from sertraline hydrochloride in bulk drug and tablet. Research Journal of Pharmacy and Technology. 2013; 6(2): 195-199.
25. Mahajan PS, Burke Jr TR. Synthetic approaches to a key pyridone-carboxylic acid precursor common to the HIV-1 integrase strand transfer inhibitors dolutegravir, bictegravir, and cabotegravir. Organic Process Research and Development. 2023; 27(5): 847-53. doi.org/10.1016/j.abb.2024.110071
26. Menéndez-Arias L, Delgado R. Update and latest advances in antiretroviral therapy. Trends in Pharmacological Sciences. 2022; 43(1): 16-29. doi.org/10.1016/j.tips.2021.10.004
27. Madhavi S, Prameela Rani A. Development and validation of RP-UPLC method for simultaneous estimation of cobicistat and darunavir. Research Journal of Pharmacy and Technology. 2017; 10(12): 4343-4349. doi.org/10.5958/0974-360X.2017.00796
28. Thakare B, Mittal A, Charde MS. Validated stability-indicating assay UHPLC method for simultaneous estimation of doravirine, lamivudine, and tenofovir disoproxil fumarate in pure material and pharmaceutical matrix. Biointerface Research in Applied Chemistry. 2022. doi.org/10.33263/BRIAC131.020
29. Nannou C, Ofrydopoulou A, Evgenidou E, Heath D, Heath E, Lambropoulou D. Analytical strategies for the determination of antiviral drugs in the aquatic environment. Trends in Environmental Analytical Chemistry. 2019. doi.org/10.1016/j.teac.2019.e00071
30. Ahmed F, et al. Principles and applications of ultra-high-performance liquid chromatography. High Performance Liquid Chromatography - Recent Advances and Applications. IntechOpen. 2023. doi.org/10.5772/intechopen.110540
31. Ganji S, Satyavati D. Development and validation of RP-HPLC method for the analysis of cobicistat and related impurities in bulk and pharmaceutical dosage forms. Asian Journal of Pharmaceutical Analysis. 2015; 5(1): 1-8. doi.org/10.5958/2231-5675.2015.00001.0
32. Satya Venkata Sakuntala M, Lakshmana Rao A, William Carey M. Stability-indicating method development and validation for the concurrent determination of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide by UPLC in bulk and tablet dosage forms. Futur J Pharm Sci. 2021; 7: 236. doi.org/10.1186/s43094-021-00384-3