“A REVIEW ON ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF DAPAGLIFLOZIN: A COMPREHENSIVE REVIEW”
Main Article Content
Keywords
Dapagliflozin, Sodium–glucose cotransporter-2 (SGLT2) inhibitors, Antidiabetic drug, Analytical method development, Method validation, International Council for Harmonisation (ICH) guidelines, Pharmaceutical analysis.
Abstract
Dapagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, is widely prescribed for the management of type 2 diabetes mellitus due to its novel mechanism of promoting renal glucose excretion and improving glycemic control. With its growing clinical use and the availability of multiple fixed-dose combinations, the need for reliable, validated analytical methods to support drug development, formulation, quality control, and regulatory compliance has increased significantly. This comprehensive review summarizes the various analytical techniques reported for dapagliflozin, including UV-spectrophotometry, RP-HPLC, UPLC, LC-MS/MS, and stability-indicating assays.
The article discusses the application of these methods in bulk drug and dosage form assay, simultaneous estimation in combination formulations, forced-degradation and stability studies, impurity profiling, bioanalytical quantification in plasma for pharmacokinetic studies, and dissolution testing. Validation parameters such as linearity, precision, accuracy, sensitivity (LOD/LOQ), robustness, and specificity, as outlined by ICH guidelines, are highlighted across reported methods. Special emphasis is given to stability-indicating methods that separate dapagliflozin from its degradants under acid, base, oxidative, photolytic, and thermal conditions.
Despite the effectiveness of conventional methods, challenges such as the use of phosphate buffers and large volumes of toxic organic solvents raise concerns about instrument damage, operator safety, cost, and environmental sustainability. To overcome these limitations, emerging trends focus on developing greener, eco-friendly, and high-throughput analytical approaches.
In conclusion, the review provides an updated and detailed insight into existing analytical strategies for dapagliflozin, while also emphasizing the future need for simple, robust, cost-effective, and environmentally sustainable methods. These advancements will play a crucial role in ensuring the safe and efficient use of dapagliflozin in pharmaceutical development, routine quality control, and clinical research.
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2. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9733):2223-33.
3. Kasichayanula S, Liu X, Pe Benito M, Yao M, Pfister M, LaCreta FP, et al. The influence of kidney function on dapagliflozin exposure, metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus. Br J Clin Pharmacol. 2013;76(3):432-44.
4. Obermeier, M1 ; Yao, M2 ; Meng, W7 ; Ellsworth, B. A7 ; Whaley, J. M6 ; Humphreys, W. G2 ; Khanna, A1 ; Koplowitz, B1 ; Zhu, M2 ; Li, W2 ; Komoroski, B4 ; Kasichayanula, S5 ; Discenza, L3 ; Washburn, W7 In Vitro Characterization and Pharmacokinetics of Dapagliflozin (BMS-512148), a Potent Sodium-Glucose Cotransporter Type II Inhibitor, in Animals and Humans. Drug Metab-Dispos. 2010;38(3):405-14.
5. Stark Casagrande S., Fradkin J., Saydah S., Rust K., Cowie C. (2013) The prevalence of meeting A1C, blood pressure, and LDL goals among people with diabetes, 1988–2010. Diabetes Care 36: 2271–2279.
6. Gomez-Peralta F, Abreu C, Lecube A, Bellido D, Soto A, Morales C, et al. Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes. Diabetes Ther. 2017;8(5):953-62.
7. Kasichayanula S, Chang M, Hasegawa M, Liu X, Yamahira N, LaCreta FP, et al. Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab. 2011;13(4):357-65.
8. Jani BR, Shah KV, Kapupara PP. Development and validation of UV spectroscopic first derivative method for simultaneous estimation of dapagliflozin and metformin hydrochloride in synthetic mixture. J Bioequiv Availab. 2015;7(6):288-93.
9. Manasa S, Dhanalakshmi K, Reddy NG, Srinivasa S. Method development and validation of dapagliflozin in API by RP-HPLC and UV-spectroscopy. Int J Pharm Sci Drug Res. 2014;6(3):250-2.
10. Chitra KP, Eswaraiah MC, Rao MV. Unique UV spectrophotometric method for reckoning of dapagliflozin in bulk and pharmaceutical dosage forms. J Chem Pharm Res. 2015;7(9):45-9.
11. Karlsson EM, Naggar AH, Alterud Z, Derendorf H. Pharmacokinetics and pharmacodynamics of dapagliflozin in patients with type 2 diabetes mellitus. Clin Pharmacokinet. 2012;51(5):295-304.
12. Gomez-Peralta F, Abreu C, Lecube A, Bellido D, Soto A, Morales C, et al. Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes. Diabetes Ther. 2017;8(5):953-62.
13. Kasichayanula S, Chang M, Hasegawa M, Liu X, Yamahira N, LaCreta FP, et al. Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab. 2011;13(4):357-65.
14. Jani BR, Shah KV, Kapupara PP. Development and validation of UV spectroscopic first derivative method for simultaneous estimation of dapagliflozin and metformin hydrochloride in synthetic mixture. J Bioequiv Availab. 2015;7(6):288-93.
15. Manasa S, Dhanalakshmi K, Reddy NG, Srinivasa S. Method development and validation of dapagliflozin in API by RP-HPLC and UV-spectroscopy. Int J Pharm Sci Drug Res. 2014;6(3):250-2.
16. Chitra KP, Eswaraiah MC, Rao MV. Unique UV spectrophotometric method for reckoning of dapagliflozin in bulk and pharmaceutical dosage forms. J Chem Pharm Res. 2015;7(9):45-9.
17. Karlsson EM, Naggar AH, Alterud Z, Derendorf H. Pharmacokinetics and pharmacodynamics of dapagliflozin in patientswith type 2 diabetes mellitus. Clin Pharmacokinet. 2012;51(5):295-304.
18. Gomez-Peralta F, Abreu C, Lecube A, Bellido D, Soto A, Morales C, et al. Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes. Diabetes Ther. 2017;8(5):953-62.
19. Kasichayanula S, Chang M, Hasegawa M, Liu X, Yamahira N, LaCreta FP, et al. Pharmacokinetics and pharmacodynamics
20. of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab. 2011;13(4):357-65.
21. Jani BR, Shah KV, Kapupara PP. Development and validation of UV spectroscopic first derivative method for simultaneous estimation of dapagliflozin and metformin hydrochloride in synthetic mixture. J Bioequiv Availab. 2015;7(6):288-93.
22. Manasa S, Dhanalakshmi K, Reddy NG, Srinivasa S. Method development and validation of dapagliflozin in API by RP- HPLC and UV-spectroscopy. Int J Pharm Sci Drug Res. 2014;6(3):250-2.
23. Chitra KP, Eswaraiah MC, Rao MV. Unique UV spectrophotometric method for reckoning of dapagliflozin in bulk and pharmaceutical dosage forms. J Chem Pharm Res. 2015;7(9):45-9.
24. Karlsson EM, Naggar AH, Alterud Z, Derendorf H. Pharmacokinetics and pharmacodynamics of dapagliflozin in patients with type 2 diabetes mellitus. Clin Pharmacokinet. 2012;51(5):295-304.
25. Gomez-Peralta F, Abreu C, Lecube A, Bellido D, Soto A, Morales C, et al. Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes. Diabetes Ther. 2017;8(5):953-62.
26. Kasichayanula S, Chang M, Hasegawa M, Liu X, Yamahira N, LaCreta FP, et al. Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab. 2011;13(4):357-65.
27. Jani BR, Shah KV, Kapupara PP. Development and validation of UV spectroscopic first derivative method for simultaneous estimation of dapagliflozin and metformin hydrochloride in synthetic mixture. J Bioequiv Availab. 2015;7(6):288-93.
28. Manasa S, Dhanalakshmi K, Reddy NG, Srinivasa S. Method development and validation of dapagliflozin in API by RP-HPLC and UV-spectroscopy. Int J Pharm Sci Drug Res. 2014;6(3):250-2.
29. Chitra KP, Eswaraiah MC, Rao MV. Unique UV spectrophotometric method for reckoning of dapagliflozin in bulk and pharmaceutical dosage forms. J Chem Pharm Res. 2015;7(9):45-9.
30. Karlsson EM, Naggar AH, Alterud Z, Derendorf H. Pharmacokinetics and pharmacodynamics of dapagliflozin in patients with type 2 diabetes mellitus. Clin Pharmacokinet. 2012;51(5):295-304.
31. Gomez-Peralta F, Abreu C, Lecube A, Bellido D, Soto A, Morales C, et al. Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes. Diabetes Ther. 2017;8(5):953-62.
32. Kasichayanula S, Chang M, Hasegawa M, Liu X, Yamahira N, LaCreta FP, et al. Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab. 2011;13(4):357-65.
33. Jani BR, Shah KV, Kapupara PP. Development and validation of UV spectroscopic first derivative method for simultaneous estimation of dapagliflozin and metformin hydrochloride in synthetic mixture. J Bioequiv Availab. 2015;7(6):288-93.
34. Manasa S, Dhanalakshmi K, Reddy NG, Srinivasa S. Method development and validation of dapagliflozin in API by RP-HPLC and UV-spectroscopy. Int J Pharm Sci Drug Res. 2014;6(3):250-2.
35. Chitra KP, Eswaraiah MC, Rao MV. Unique UV spectrophotometric method for reckoning of dapagliflozin in bulk and pharmaceutical dosage forms. J Chem Pharm Res. 2015;7(9):45-9.
36. Karlsson EM, Naggar AH, Alterud Z, Derendorf H. Pharmacokinetics and pharmacodynamics of dapagliflozin in patients with type 2 diabetes mellitus. Clin Pharmacokinet. 2012;51(5):295-304.
37. Gomez-Peralta F, Abreu C, Lecube A, Bellido D, Soto A, Morales C, et al. Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes. Diabetes Ther. 2017;8(5):953-62.
38. Kasichayanula S, Chang M, Hasegawa M, Liu X, Yamahira N, LaCreta FP, et al. Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab. 2011;13(4):357-65.
39. Jani BR, Shah KV, Kapupara PP. Development and validation of UV spectroscopic first derivative method for simultaneous estimation of dapagliflozin and metformin hydrochloride in synthetic mixture. J Bioequiv Availab. 2015;7(6):288-93.
40. Manasa S, Dhanalakshmi K, Reddy NG, Srinivasa S. Method development and validation of dapagliflozin in API by RP-HPLC and UV-spectroscopy. Int J Pharm Sci Drug Res. 2014;6(3):250-2.
41. Chitra KP, Eswaraiah MC, Rao MV. Unique UV spectrophotometric method for reckoning of dapagliflozin in bulk and pharmaceutical dosage forms. J Chem Pharm Res. 2015;7(9):45-9.
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Sep 26, 2025
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Dhruvi V Patel, Dr. Neha Tiwari, & Dr. Pragnesh Patani. (2025). “A REVIEW ON ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF DAPAGLIFLOZIN: A COMPREHENSIVE REVIEW”. Journal of Population Therapeutics and Clinical Pharmacology, 32(7), 1677-1686. https://doi.org/10.53555/rrykrb89
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Author Biographies
Dhruvi V Patel
Department of Pharmaceutical Quality Assurance, Khyati College of Pharmacy, Ahmedabad, Gujarat, India.
Dr. Neha Tiwari
Department of Pharmaceutical Chemistry, Khyati College of Pharmacy, Ahmedabad, Gujarat, India.
Dr. Pragnesh Patani
Department of Pharmacology, Khyati College of Pharmacy, Ahmedabad, Gujarat, India.
How to Cite
Dhruvi V Patel, Dr. Neha Tiwari, & Dr. Pragnesh Patani. (2025). “A REVIEW ON ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF DAPAGLIFLOZIN: A COMPREHENSIVE REVIEW”. Journal of Population Therapeutics and Clinical Pharmacology, 32(7), 1677-1686. https://doi.org/10.53555/rrykrb89