Author(s):
Amitkumar J. Vyas, Drashti J. Gajjar, Saurabh S. Ray, Ajay I. Patel, Ashvin V. Dudhrejiya, Devang B. Sheth, Ashok B. Patel, Sunny R. Shah
Email(s):
drashtigajjar5577@gmail.com
DOI:
10.52711/0974-360X.2025.00684 
Address:
Amitkumar J. Vyas1, Drashti J. Gajjar*1, Saurabh S. Ray1, Ajay I. Patel1, Ashvin V. Dudhrejiya1, Devang B. Sheth2, Ashok B. Patel2, Sunny R. Shah3
1B. K. Mody Government Pharmacy College, Gujarat Technological University, Rajkot, India.
2L. M. College of Pharmacy, Gujarat Technological University, Ahmedabad, India.
3Government Pharmacy College, Gujarat Technological University, Gandhinagar, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 10,
Year - 2025
ABSTRACT:
A stability indicating method for estimation of Voxelotor in tablet dosage form was developed. The method was optimised for sufficient resolution between drug peak and degradant peak. For this mobile phase of (MeOH: H2O) was selected in the ratio (75:25). The method was stressed under various conditions such as Acid and Base hydrolysis, Oxidative, Photolytic, and Thermal degradation. The method showed maximum tolerance against acid hydrolysis and minimum tolerance against base hydrolysis. The method was validated according to ICH guidelines Q2(R1).
Cite this article:
Amitkumar J. Vyas, Drashti J. Gajjar, Saurabh S. Ray, Ajay I. Patel, Ashvin V. Dudhrejiya, Devang B. Sheth, Ashok B. Patel, Sunny R. Shah. Stability Indicating RP-HPLC Method for Estimation of Voxelotor for the Treatment of Sickle Cell Disease. Research Journal of Pharmacy and Technology. 2025;18(10):4759-4. doi: 10.52711/0974-360X.2025.00684
Cite(Electronic):
Amitkumar J. Vyas, Drashti J. Gajjar, Saurabh S. Ray, Ajay I. Patel, Ashvin V. Dudhrejiya, Devang B. Sheth, Ashok B. Patel, Sunny R. Shah. Stability Indicating RP-HPLC Method for Estimation of Voxelotor for the Treatment of Sickle Cell Disease. Research Journal of Pharmacy and Technology. 2025;18(10):4759-4. doi: 10.52711/0974-360X.2025.00684 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-10-23
REFERENCES:
1. Reappraisal of known malaria resistance loci in a large multicentre study. Nature Genetics. 2014; 46(11): 1197-1204. https://doi.org/10.1038/ng.3107
2. Scott, J. Anthony G., et al. Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study. The Lancet. 2011; 378(9799): 1316-1323. https://doi.org/10.1016/S0140-6736(11)60888-X
3. Piel, Frédéric B., et al. Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nature Communications. 2010; 1(1): 104. https://doi.org/10.1038/ncomms1104
4. Piel, Frédéric B., et al. Global migration and the changing distribution of sickle haemoglobin: a quantitative study of temporal trends between 1960 and 2000. The Lancet Global Health. 2014; 2(2): e80- e89. https://doi.org/10.1016/S2214-109X(13)70150-5
5. Hassell, Kathryn L. Population estimates of sickle cell disease in the US. American Journal of Preventive Medicine. 2010; 38(4): S512- S521.https://doi.org/10.1016/j.amepre.2009.12.022
6. Piel, Frédéric B., et al. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. The Lancet. 2013; 381(9861): 142-151. https://doi.org/10.1016/S0140- 6736(12)61229-X
7. Williams, Thomas N., and Swee Lay Thein. Sickle cell anemia and its phenotypes. Annual Review of Genomics and Human Genetics. 2018; 19: 113-147.
8. Oxbryta. Package insert. Global Blood Therapeutics, Inc; 2019.
9. Herity, Leah B., et al. Voxelotor: a novel treatment for sickle cell disease. Annals of Pharmacotherapy. 2021; 55(2): 240245. https://doi.org/10.1177/1060028020943059
10. Dufu, Kobina., et al. GBT440 improves red blood cell deformability and reduces viscosity of sickle cell blood under deoxygenated conditions. Clinical Hemorheology and Microcirculation. 2018; 70(1): 95-105. https://doi.org/10.3233/CH-170340
11. Howard, Jo., et al. A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease. Blood, The Journal of the American Society of Hematology. 2019; 133(17): 1865-1875. https://doi.org/10.1182/blood-2018-08-868893
12. Blair, Hannah A. Voxelotor: first approval. Drugs. 2020; 80(2): 209-215. https://doi.org/10.6084/m9.figshare 11658999.v1
13. Taviyad, Mittal., et al. Chromatographic Method Development And Validation For Related Substance. Pharma Science Monitor. 2017; 8(2).
14. Kishna Ram, Swati Guttikar., et al. Rapid, sensitive and simple lc-ms/ms method development and validation for estimation of phenytoin in human plasma by using deuterated internal standard. Research Journal of Pharmacy and Technology. 2021; 14(6): 2937-2944. http://dx.doi.org/10.52711/0974-360X.2021.00515.
15. Snyder, Lloyd R., Joseph J. Kirkland, and Joseph L. Glajch. Practical HPLC method development. John Wiley and Sons. 2012.
16. Sethi PD. HPLC Qualitative analysis of pharmaceutical formulation; CBS Publication and Distributors, New Delhi. 2000. 101-105.
17. Chatwal GR., Sham AK. Instrumental Methods of Analysis, 5th edition. Himalaya Publishing House, New Delhi. 2002; 2: 624- 625.
18. ICH-Harmonized Tripartite Guideline, Stability Testing of New Drug Substances and Products; QIA (R2), 2005.
19. ICH- Harmonized Tripartite Guideline, Photo Stability testing of New Drug Substance and product: ICH Q1 C, 2006.
20. Ahuja S, Rasmussen H. HPLC method development for Pharmaceuticals. 2007.
21. Singh S, Bakshi M. Guidance on Conduct of Stress Tests to Determine Inherent Stability of Drugs. Pharmaceutical Technology on-line, 2000, 1–14.
22. Steven WB, Karen MA, Robert AR. Pharmaceutical stress testing; 2nd edition; Informa healthcare.
23. P. Sneha and Prathima Srinivas. Stability indicating assay method development and validation of pregabalin in pharmaceutical dosage forms by RP-HPLC. Indo American J of Pharm Sci. 2015; 2(6): 1038–47.
24. Nagaraju KS, Rao BS, Kiran BV. Development, Validation and Stress Degradation Studies of Pregabalin By High Performance Liquid Chromatography. Int J. Pharma Sci. Res. 2013; 4(7): 2782–2788.
25. Brian M and Chihyuan C. Substituted benzaldehyde compounds and methods for their use in increasing tissue oxygenation. United States Patents US 9018210 B2, 2015.
26. Zhe L, Stephan D and Tavis H. Crystalline polymorphs of the free base of 2-hydroxy- 6-((2-(1-isopropyl-1h-pyrazol-5-yl)-pyridin-3-yl) methoxy) benzaldehyde. United States Patents US 9447071 B2, 2016.
27. Sean M, Naveen B, Nazila H, Ali K and DeMei L. Tablets comprising 2-hydroxy-6- ((2-(1-isopropyl-1H-pyrazol-5-yl) pyridin-3-yl) methoxy) benzaldehyde. United States Patents US 10493035 B2, 2019.
28. Zhe L, Stephan D and Tavis H. Crystalline polymorphs of the free base of 2-hydroxy- 6-((2-(1-isopropyl-1H-pyrazol-5-yl) pyridin-3-yl) methoxy) benzaldehyde. United States Patents US 10722502 B2, 2020.
29. Zhe L, Stephan D and Tavis H. Crystalline polyorphs of the free base of 2-hydroxy- 6-((2-(1-isopropyl-1h-pyrazol-5-yl) pyridin-3-yl) methoxy) benzaldehyde. United States Patents US 11452720 B2, 2022.
30. National Centre for Biotechnology Information. “PubChem Compound Summary for CID 71602803, Voxelotor”, 2004.https://pubchem.ncbi.nlm.nih.gov/compound/Voxelotor
31. Buya, Aristote B., Romano Terrasi, Jérémie K. Mbinze, Giulio G. Muccioli, Ana Baroque, Patrick B. Memvanga, and Véronique Préat. Quality-by-design-based development of a voxelotor self-nanoemulsifying drug-delivery system with improved biopharmaceutical attributes. Pharmaceutics. 2021; 13(9): 1388. https://doi.org/10.3390/pharmaceutics13091388
32. Neelam, Uday Kumar, Bhatraju Daveedu, Vekariya Nagaji Ambabhai, Mahender Rao Siripragada, and Sridhar Balasubramanian. Physicochemical aspects and comparative analysis of Voxelotor and its salt and cocrystal. Journal of Molecular Structure. 2023; 1271: 134024. https://doi.org/10.1016/j.molstruc.2022.134024.
33. Shailesh S. Chalikwar, Kailas K. Moravakar, Bhushan A. Bhairav. Stability Indicating Method Development and Validation for Estimation of Valacyclovir in Pharmaceutical Preparation. Asian Journal of Pharmaceutical Analysis. 2024; 14(2): 53-9. DOI: 10.52711/2231-5675.2024.00010
34. S. Ashutosh Kumar, Manidipa Debnath, J.V.L.N. Seshagiri Rao, D. Gowri Sankar. Stability indicating Method Development and Validation for simultaneous estimation of Hydrochlorothiazide, Amlodipine and Olmesartan in tablet dosage form by using RP-HPLC. Asian J. Research Chem. 2014; 7(5): 538-548.
35. Shinde G. S., Jadhav R. S., Vikhe D. N. Stability indicating Method development and Validation of Lamivudine, Zidovudine and Nevirapinein Tablet dosage form. Research Journal of Pharmaceutical Dosage Forms and Technology. 2022; 14(3): 238-4. DOI: 10.52711/0975-4377.2022.00039
36. Rathod N., et al. Analytical Method Development and Validation of Stability Indicating Method and Related Substance by Using RP-HPLC Of Drug Substance. Pharma Science Monitor Year: 2017; 8 (2): 409-419.
37. Chirag D. Jadav, et al. Review on Stability Indicating Assay Method or Forced Degradation study: Strategy and Regulatory Consideration. 2023; 13(2): 131-139. DOI: 10.52711/2231-5675.2023.00022
38. Dhruvi U Parmar, et al. Strategic approach for HPLC method Development and validation: Review. 2023; 14(1): 71-76. DOI: 10.52711/2231- 5659.2024.00011
39. Shalini A. Jha, et al.: Review on simultaneous equation method (Vierodt's method). Asian Journal of Pharmaceutical Analysis. 2022; 12(2). DOI: 10.52711/2231-5675.2022.00026
40. Harshal M. Vadile, et al. Recent Applications Of UV-Visible Derivative Spectroscopic Method. 2023; 13(2). DOI: 10.52711/2231-5675.2023.00019
41. Brijesh H Patel, et al. A brief review on q-absorption ratio method in UV- spectrophotometry. Asian Journal of Pharmaceutical Analysis. 2022; 12(4): 281-285. DOI: 10.52711/2231-5675.2022.00046
42. Sonali B. Mishra, et al. A Brief Review on Liquid Chromatography- Mass Spectrometry/LCMS and its Application. Asian Journal of Pharmaceutical Analysis. 2022; 12(3): 203-210. DOI: 10.52711/2231-5675.2022.00034
43. Anjana Vaghela, et al. Sample preparation in bioanalysis: a review. International Journal of Scientific and Technology Research. 5(5): 6-10.
44. Asnani A.H, et al.. A brief review on genotoxic impurities in pharmaceuticals. Asian Journal of Pharmaceutical Research. 2021; 11(3). DOI: 10.52711/2231-5691.2021.00034
45. Godhaniya, J.P, et al. A review on carcinogenic impurities found in marketed drugs and strategies for its determination by analytical methods. Asian Journal of Pharmaceutical Analysis. 2021; 11(2): 159-169. DOI: 10.52711/2231-5675.2021.00028
46. Bundheliya et al. A Review on Metal Impurities in Pharmaceuticals. Asian Journal of Pharmaceutical Analysis. 2021; 11(3): 212-222. DOI: 10.52711/2231-5675.2021.00038
47. Anjali K. Mandavia, et al. Nitrosamine Impurity: Management of Unwelcome Guest in Pharma Market. 2023; 13(4): 303-308. DOI: 10.52711/2231-5675.2023.00049
48. Patel S.M, et al. Stability testing: An Essential study for Vaccine Formulation Development. Asian Journal of Pharmaceutical Research. 2022; 12(1): 29-36. DOI: 10.52711/2231-5691.2022.00006
49. K. Sonia, M. Nappinnai, P. Panneerselvam. Stability indicating Method Development and Validation of Telmisartan and Ramipril by UV Spectrophotometry.Research J. Pharm. and Tech. 2018; 11(7): 3087-3090. DOI: 10.5958/0974-360X.2018. 00567.X
50. Merugu Manasa, Vijey Aanandhi M. Stability Indicating Method Development and Validation of Semaglutide by RP-HPLC in Pharmaceutical substance and Pharmaceutical Product. Research J. Pharm. and Tech. 2021; 14(3): 1385-1389. DOI: 10.5958/0974-360X.2021. 00247.X
51. Kishore Konam, Somasekhar Reddy Kanala. A Stability Indicating Method Development and Validation for The Simultaneous Estimation of Emtricitabine, Tenofovir Alafenamide and Doultegravir in Pharmaceutical Formulation by Ultra Performance Liquid Chromatography. Research Journal of Pharmacy and Technology. 2021; 14(11): 6017-4. DOI: 10.52711/0974-360X.2021.01046
52. A. Indira, N. Y. Sreedhar, D. Balakrishna. A Stability Indicating Method Development of Lopinavir and Rotinavir in Combined Tablet Dosage Forms by RP-HPLC. Research Journal of Pharmacy and Technology. 2022; 15(2): 661-4. DOI: 10.52711/0974-360X.2022.00109
53. Visana N.M, et al. Analytical quality by design in stress testing or stability- indicating method. Asian Journal of Pharmaceutical Analysis. 2021; 11(2): 170-178. DOI: 10.52711/2231-5675.2021.00029
54. Gol Dhruvanshi, et al. Implementing Analytical Quality by Design (AQbD) Approach for Simultaneous Estimation of Tadalafil and Macitentan by RP-HPLC Method. Analytical Chemistry Letters. 2021; 11(4): 539-552. DOI:10.1080/22297928.2021.1938215
55. Prajapati Krupa, et al. RP-HPLC Method for Determination of Gemifibrozil using Central composite design (CCD). Research Journal of Pharmacy and Technology. 2021; 14(6): 3009- 3014. DOI: 10.52711/0974-360X.2021.00527
56. Alkindi S., et al. Influence of Voxelotor–hemoglobin complexes in the estimation of hemoglobin S levels by the current standard of care laboratory evaluation techniques. Frontiers in Medicine. 2023; 10: 1149281.