Bandaru Sai Pavan Kumar and Mukthinuthalapati Mathrusri Annapurna*

Department of Pharmaceutical Analysis, GITAM School of Pharmacy, Gandhi Institute of Technology and Management (Deemed to be University), Visakhapatnam, India

*Corresponding Author: Mukthinuthalapati Mathrusri Annapurna, Department of Pharmaceutical Analysis, GITAM School of Pharmacy, Gandhi Institute of Technology and Management (Deemed to be University), Visakhapatnam, India.

Received: September 30, 2022; Published: October 27, 2022

Abstract

Emtricitabine, Tenofovir disoproxil fumarate and Dolutegravir sodium are anti-HIV drugs. The authors have developed a new stability indicating RP-UPLC method for the simultaneous determination of Emtricitabine, Tenofovir disoproxil fumarate and Dolutegravir sodium in tablets on gradient mode using a mixture of mobile phase A (0.1% Tri ethyl amine pH adjusted to 4.5 ± 0.05 with ortho phosphoric acid) and mobile phase B (0.1% Tri fluoro acetic acid in acetonitrile) with 1.0 mL/min flow rate are the chromatographic conditions for the entire study. Shimadzu NexeraX2 Model UPLC system with PDA detector Zorbax column (100 mm × 4.60 mm, 3.5 μ) was employed for the present study. Beer-Lambert’s law was obeyed over the concentration range 2-600, 2-900 and 1-150 µg/mL with linear regression equation y = 1226.8x - 160.82 (R² = 0.9999), y = 1200.3x - 1540.5 (R² = 0.9999) and y = 3214x + 693.63 (R² = 0.9999) for Emtricitabine, Tenofovir disoproxil fumarate and Dolutegravir sodium and the method was validated as per ICH guidelines. The LOQ values were found to be 1.8231, 1.9014 and 0.9243 µg/mL and that of LOD values as 0.6002. 0.6259 and 0.3039 µg/mL for Emtricitabine, Tenofovir disoproxil fumarate and Dolutegravir sodium respectively. The combination of Tenofovir Disoproxil Fumarate, Dolutegravir sodium and Emtricitabine was exposed to various stress conditions and the stability of the proposed method was carried out at UV detection 260 nm. The proposed RP-UPLC method is simple, precise, accurate, robust and used for the routine analysis of tablet dosage forms.

Keywords: UPLC; Stability Indicating; Emtricitabine; Tenofovir Disoproxil Fumarate; Dolutegravir Sodium

References

1. Miller MD., et al. “Antiviral activity of Tenofovir against nucleoside-resistant clinical HIV samples”. Nucleosides Nucleotides Nucleic Acids4-7 (2001): 1025-1028.
2. Uglietti A., et al. “Emtricitabine/Tenofovir in the treatment of HIV infection: current PK/PD evaluation”. Expert Opinion on Drug Metabolism and Toxicology 10 (2012): 1305-1314.
3. Katlama C and Murphy R. “Dolutegravir for the treatment of HIV”. Expert Opinion on Investigational Drugs 4 (2012): 523-530.
4. Min S., et al. “Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1 infected adults”. AIDS14 (2011): 1737-1745.
5. Sudha T., et al. “Simultaneous ultraviolate spectrophotometric estimation of Emtricitabine and Tenofovir disopoxil fumarate in bulk and tablet dosage form”. International Journal of Bio-Pharma Research 1 (2010): 26-30.
6. Delahunty T., et al. “The Simultaneous assay of Tenofovir and Emtricitabine in plasma using LC/MS/MS and isotopically labelled internal standards”. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 877 (2009): 20-21. 
7. Rao J., et al. “Simultaneous HPTLC-Densitometric analysis of Tenofovir and Emtricitabine in Tablet dosage form”. International Journal of PharmTech Research 3 (2011): 1430-1434. 
8. Sharma R and Gupta P. “A validated RP-HPLC method for simultaneous estimation of Emtricitabine and Tenofovir disoproxil fumarate in a tablet dosage form”. EJAC 4 (2009): 276-278. 
9. Sharma R and Mehta K. “Simultaneous Spectrophotometric estimation of Tenofovir disoproxil fumarate and Lamivudine in three component tablet formulation containing Efavirenz”.Indian Journal of Pharmaceutical Sciences 72 (2010): 527-530. 
10. Anandakumar K., et al. “RP-HPLC method for simultaneous estimation of Lamivudine, Tenofovir disoproxil fumarate and Efavirenz in tablet formulation”. Journal of Analytical Chemistry 68 (2018): 815-821.
11. Ramreddy G., et al. “Concurrent estimation of Lamivudine, Tenofovir disoproxil fumarate, and Efavirenz in blended mixture and triple combination tablet formulation by a new stability indicating RP-HPLC method”.Future Journal of Pharmaceutical Sciences 7 (2021): 94.
12. Bhavsar DS., et al. “RP-HPLC method for simultaneous estimation of Tenofovir disoproxil fumarate, Lamivudine and Efavirenz in combined tablet dosage form”. Pharmaceutical Methods2 (2012): 73-78.
13. Nekkala K. “Development and validation for the simultaneous estimation of Lamivudine, Tenofovir disproxil and Dolutegravir in drug product by RP-HPLC”. Journal of Pharmaceutical Sciences and Research 9 (2017): 6.
14. Mallikarjuna Rao N and Gowri Sankar D. “Development and validation of stability-indicating HPLC method for simultaneous determination of Lamivudine, Tenofovir, and Dolutegravir in bulk and their tablet dosage form”. Future Journal of Pharmaceutical Sciences 2 (2015): 73-77.
15. Jagadabi V., et al. “A stability-indicating HPLC method for the determination of potential impurities in a few fixed dose combination of Dolutegravir, Lamivudine and Tenofovir disoproxil fumarate tablets used in the first line treatment of HIV-1 infection”. International Research Journal of Pharmacy 5(2018): 65-74.
16. Saravanan R., et al. “Analytical method development and validation of stability indicating assay method of analysis for Dolutegravir/Lamivudine/Tenofovir Disoproxil fumarate tablets using high performance liquid chromatography”. Research Journal of Pharmacy and Technology5 (2021): 2434-2439.
17. Raju N and Begum S. “Simultaneous RP-HPLC method for the estimation of the Emtricitabine, Tenofovir disoproxil fumerate and Efavirenz in tablet dosage forms”.Research Journal of Pharmacy and Technology 1 (2008): 522-525.
18. Ramaswamy A and Arul Gnana Dhas AS. “Development and validation of analytical method for quantitation of Emtricitabine, Tenofovir, Efavirenz based on HPLC”. Arabian Journal of Chemistry2(2018): 275-281.
19. Rezaei Mehdi., et al. “Simultaneous estimation and validation of Tenofovir disoproxil fumarate, Emtricitabine and Efavirenz by RP-HPLC method in combined tablet dosage form”. Current Pharmaceutical Analysis6 (2019): 561-567.
20. ICH Validation of analytical procedures: Text and methodology Q2 (R1), International Conference on Harmonization (2005).
21. ICH Stability testing of new drug substances and products Q1A (R2), International Conference on Harmonization (2003).

Citation

Citation: Bandaru Sai Pavan Kumar and Mukthinuthalapati Mathrusri Annapurna. “Development and Validation of a New Stability Indicating RP-UPLC Method for the Simultaneous Estimation of Anti-Viral Drugs: Tenofovir Disoproxil Fumarate, Emtricitabine and Dolutegravir (Tablets)". Acta Scientific Pharmaceutical Sciences 6.11 (2022): 18-27.

Copyright

Copyright: © 2022 Bandaru Sai Pavan Kumar and Mukthinuthalapati Mathrusri Annapurna. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.