STABILITY INDICATING METHOD DEVELOPMENT AND VALIDATION OF METFORMIN AND ERTUGLIFLOZIN BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY WITH PDA DETECTION AND ITS APPLICATION TO TABLET DOSAGE FORM
Objective: A sensitive, rapid, accurate, and precise stability indicating high-performance liquid chromatography method was developed and validated for the simultaneous estimation of metformin (MET) and ertugliflozin (ERT).
Methods: The planned chromatographic method was developed using Kromasil C18 column using 0.1 M sodium dihydrogen phosphate methanol (50:50, by volume, pH 4.0) as mobile phase system followed by peak area response measurement at 238 nm. The developed method was validated by means of ICH guidelines about system suitability, linearity, sensitivity, selectivity, accuracy, precision, robustness, and specificity.
Results: Calibration curves of MET and ERT are linear from 250 to 750 μg/ml and 3.75 to 11.25 μg/ml, respectively. Relative standard deviation is <2.0% and recovery is ̴ 100%. Successfully, the developed method was applied for the simultaneous determination of MET and ERT in tablets and to study degradation of MET and ERT in acidic, alkaline, oxidation, thermal, and photolytic degradation conditions. No obstructions from additional common excipients of tablets and degradants were observed.
Conclusion: The results recommended method suitability for the analysis of MET and ERT in quality control laboratories.
2. From the medical letter on drugs and therapeutics. Ertugliflozin for Type 2 diabetes. JAMA 2018;319:2434-35.
3. Cinti F, Moffa S, Impronta F, Cefalo CM, Sun VA, Sorice GP, et al. Spotlight on ertugliflozin and its potential in the treatment of Type 2 diabetes: Evidence to date. Drug Des Devel Ther 2017;11:2905-19.
4. Wang YW, He SJ, Feng X, Cheng J, Luo YT, Tian L, et al. Metformin: A review of its potential indications. Drug Des Devel Ther 2017;11:2421-9.
5. Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017;60:1577-85.
6. Madiraju AK, Qiu Y, Perry RJ, Rahimi Y, Zhang XM, Zhang D, et al. Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nat Med 2018;24:1384-94.
7. Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 2014;510:542-6.
8. FDA Approves Segluromet. Available from: https://www.drugs.com/newdrugs/fda-approves-segluromet-ertugliflozin-metformin-hydrochloride-type-2-diabetes-4669.html.
9. Ertugliflozin/Metformin (By Mouth). PubMed Health, 2018. Available from: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0031142/?report=details.
10. International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceutical for Human Use Stability Testing of New Drugs Substance and Products. Geneva, Switzerland: Q1A (R2); 2003.
11. International Conference on Harmonization; Validation of Analytical Procedures: Text and Methodology, Q2 (R1). Geneva, Switzerland: IFPMA; 2005.
12. Hemant KJ, Umakant SJ. Development and validation of RP-HPLC method for estimation of darunavir ethanolate in bulk and tablets. Int J Pharm Pharm Sci 2015;7:386-9.
13. Babu GR, Rao AL, Rao JV. A rapid RP-HPLC method development and validation for the quantitative estimation ribavirin in tablets. Int J Pharm Pharm Sci 2015;7:60-3.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.