Login Register Cart 0
Generic placeholder image

Drug Metabolism and Bioanalysis Letters

Editor-in-Chief

ISSN (Print): 2949-6810
ISSN (Online): 2949-6829

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Research Article

Analytical Method Development, Validation and Forced Degradation Study of Dapagliflozin by RP-HPLC

Author(s): Ujwal Chaudhari, Jagdish K. Sahu* and Payal R. Dande

Volume 16, Issue 2, 2023

Published on: 07 September, 2023

Page: [140 - 152] Pages: 13

DOI: 10.2174/2949681016666230823091112

Price: $65

Abstract

Background: Worldwide, it is projected that 285 million individuals have diabetes, and by 2030, this number is expected to climb to 438 million. About 90% of cases of diabetes mellitus are type 2 (T2DM). Insulin sensitizers, such as metformin and thiazolidinediones; insulin secretagogues, such as sulfonylureas and glinides; dipeptidyl peptidase 4 (DPP-4) inhibitors; glucosidase inhibitors, or oral combination therapy are currently available treatments for type 2 diabetes. Some of these drugs exhibit serious limitations; thus, it is crucial to design an innovative therapy that is efficient and depends on a new channel.

Aim: In the current work, a stability-indicating reverse phase HPLC (RP-HPLC) technique was developed and subsequently validated for the detection of dapagliflozin in its API.

Methods: The stability-indicating HPLC method for assay included the use of Kromasil 100-5-C8 (100 mm × 4.6 mm) column, UV detector 224 nm, mobile phase composition involving a mixture of acetonitrile:water (52:48), and a flow rate of 1.0 mL/min. ICH guidelines were followed for the method's validation. To assess the method's specificity and stability in showing characteristics, stress degradation studies were carried out. The working standard solution of dapagliflozin was exposed to 1 and 2 N HCl by refluxing 1 and 2 N NaOH with 30% hydrogen peroxide by volume and UV radiation in order to conduct a degradation study.

Results: All system suitability parameters were determined to be within the intended ranges, and the drug's retention duration was discovered to be 1.67 minutes. It was also investigated as to how the drug degraded under various circumstances. The drug was discovered to be stable under situations of photolytic, thermal, neutral, alkaline, and oxidative deterioration. The developed stabilityindicating HPLC technique was validated in accordance with ICH Q2 recommendations, and the validation parameters, such as linearity, precision, and robustness, were achieved within the approved standards.

Conclusion: It may be concluded that this method is stability-indicating and specific, and it can be successfully applied to analyze tablet dosage forms containing dapagliflozin.

Keywords: Dapagliflozin, RP-HPLC, degradation, analytical validation, ICH guideline, T2DM.

« Previous Next »
Graphical Abstract

[1]
Kasichayanula, S.; Liu, X.; LaCreta, F.; Griffen, S.C.; Boulton, D.W. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin. Pharmacokinet., 2014, 53(1), 17-27.
[http://dx.doi.org/10.1007/s40262-013-0104-3] [PMID: 24105299]
[2]
Nasser, S.; Salama, I.; Mostafa, S.M.; Elgawish, M.S. Comparative high-performance liquid chromatographic and high-performance thin-layer chromatographic study for the simultaneous determination of dapagliflozin and metformin hydrochloride in bulk and pharmaceutical formulation. J. Planar Chromatogr. Mod. TLC, 2018, 31(6), 469-476.
[http://dx.doi.org/10.1556/1006.2018.31.6.7]
[3]
Greg, L.P. Dapagliflozin: A review of its use in type 2 diabetes mellitus. Drugs, 2012, 72(17), 2289-2312.
[4]
List, J.F.; Woo, V.; Morales, E.; Tang, W.; Fiedorek, F.T. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care, 2009, 32(4), 650-657.
[http://dx.doi.org/10.2337/dc08-1863] [PMID: 19114612]
[5]
Wilding, J.P.H.; Norwood, P.; T’joen, C.; Bastien, A.; List, J.F.; Fiedorek, F.T. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: Applicability of a novel insulin-independent treatment. Diabetes Care, 2009, 32(9), 1656-1662.
[http://dx.doi.org/10.2337/dc09-0517] [PMID: 19528367]
[6]
Tiwari, G.; Tiwari, R. Bioanalytical method validation: An updated review. Pharm. Methods, 2010, 1(1), 25-38.
[http://dx.doi.org/10.4103/2229-4708.72226] [PMID: 23781413]
[7]
Mante, G.V.; Gupta, K.R.; Hemke, A.T. Estimation of dapagliflozin from its tablet formulation by UV-spectrophotometry. Pharm. Methods, 2017, 8(2), 102-107.
[http://dx.doi.org/10.5530/phm.2017.8.16]
[8]
Kaku, K.; Maegawa, H.; Tanizawa, Y.; Kiyosue, A.; Ide, Y.; Tokudome, T.; Hoshino, Y.; Yang, J.; Langkilde, A.M. Dapagliflozin as monotherapy or combination therapy in Japanese patients with type 2 diabetes: An open-label study. Diabetes Ther., 2014, 5(2), 415-433.
[http://dx.doi.org/10.1007/s13300-014-0086-7] [PMID: 25341477]
[9]
Tahrani, A.A.; Barnett, A.H. Dapagliflozin: A sodium glucose cotransporter 2 inhibitor in development for type 2 diabetes. Diabetes Ther., 2010, 1(2), 45-56.
[http://dx.doi.org/10.1007/s13300-010-0007-3] [PMID: 22127745]
[10]
Araki, E.; Onishi, Y.; Asano, M.; Kim, H.; Ekholm, E.; Johnsson, E.; Yajima, T. Efficacy and safety of dapagliflozin in addition to insulin therapy in Japanese patients with type 2 diabetes: Results of the interim analysis of 16‐week double‐blind treatment period. J. Diabetes Investig., 2016, 7(4), 555-564.
[http://dx.doi.org/10.1111/jdi.12453] [PMID: 27181422]
[11]
Reilly, T.P.; Graziano, M.J.; Janovitz, E.B.; Dorr, T.E.; Fairchild, C.; Lee, F.; Chen, J.; Wong, T.; Whaley, J.M.; Tirmenstein, M. Carcinogenicity risk assessment supports the chronic safety of dapagliflozin, an inhibitor of sodium-glucose co-transporter 2, in the treatment of type 2 diabetes mellitus. Diabetes Ther., 2014, 5(1), 73-96.
[http://dx.doi.org/10.1007/s13300-014-0053-3] [PMID: 24474422]
[12]
Anderson, S.L. Dapagliflozin efficacy and safety: A perspective review. Ther. Adv. Drug Saf., 2014, 5(6), 242-254.
[http://dx.doi.org/10.1177/2042098614551938] [PMID: 25436106]
[13]
Venkatappa, S. An overview on analytical methods for dapagliflozin – an antidiabetic drug. Int. J. Pharm. Sci. Res., 2019, 10(6)
[http://dx.doi.org/10.13040/IJPSR.0975-8232.10(6).2688-92]
[14]
Dapagliflozin. Available from: https://go.drugbank.com/unearth/q?query=Dapagliflozine&button=&searcher=drugs
[15]
Arayne, M.S.; Sultana, N.; Zuberi, M.H.; Siddiqui, F.A.; Haroon, U. Simultaneous determination of metformin, captopril, lisinopril, and enalapril by RP-HPLC: Its applications in dosage formulations and in human serum. Med. Chem. Res., 2013, 22(12), 5717-5722.
[http://dx.doi.org/10.1007/s00044-013-0501-z]
[16]
Lakshmi, K.S.; Rajesh, T.; Sharma, S. Simultaneous determination of metformin and pioglitazone by reversed phase HPLC in pharmaceutical dosage forms. Int. J. Pharm. Pharm. Sci., 2009, 1(2), 162-166.
[17]
Umekar, M.J.; Mante, G.V.; Hemke, A.T.; Umekar, M.J. RP-HPLC method for estimation of dapagliflozin from its tablet. Int. J. Chemtech Res., 2021, 1(1), 242-248.
[18]
Suma, B.V. R, D.; Shenoy, P. A new high performance thin layer chromatographic method development and validation of dapagliflozin in bulk and tablet dosage form. Int. J. Pharm. Pharm. Sci., 2019, 11(8), 58-63.
[http://dx.doi.org/10.22159/ijpps.2019v11i8.34339]
[19]
Patel, T.; Parikh, R. Method development, validation and forced degradation studies of dapagliflozin and pioglitazone hydrochlorides in synthetic mixtures by RP-HPLC. Int. J. Trend Sci. Res. Dev., 2022, 6(6), 1858-1869.
[20]
Sahu, J.K.; Agrawal, A.A.; Dawre, S.; Kanugo, A. Determination of olmesartan in bulk and pharmaceutical dosage forms through the development and validation of stability-indicating RP-HPLC method. Drug Metab. Bioanal. Lett., 2023, 16(1), 65-72.
[http://dx.doi.org/10.2174/2949681016666230224153822]

Rights & Permissions Print Cite
Article Metrics
20
2
© 2024 Bentham Science Publishers | Privacy Policy