Development and validation of UPLC-MS/MS method for estimation of Saxagliptin in bulk and tablet dosage forms

Abstract

Background and Aims: Saxagliptin is an antidiabetic drug used to treat type 2 diabetes mellitus. During the manufacture of bulk and dosage forms, assay of the drugs is important in determining the percentage purity. Hence, this study aimed to develop and validate a simple, rapid, and selective method based on ultra-performance liquid chromatography-Tandem mass spectrometry (UPLC-MS/MS) analysis for the determination of saxagliptin in bulk and tablet dosage forms. Methods: Chromatographic separation was performed using a Waters Acquity UPLC BEH C18 column (2.1 X 50 mm, 1.7 μm) with a mobile phase consisting of a mixture of acetonitrile: 0.1% formic acid (60:40, v/v) at a flow rate of 0.120 mL/min. Separation was performed in 3 min run time. The analyte was ionised and detected by tandem mass spectrometry, which is performed in positive ion and multiple reaction monitoring modes. Results: Linearity was established in the 10–150 ng/mL with r2=0.9980. The results were observed to be well within the limits when validation was performed as per the ICH guidelines. Conclusion: The proposed method can be applied successfully for the analysis of saxagliptin in bulk and tablet formulations.

Keywords

• Saxagliptin
• UPLC-MS/MS
• Method development
• Validation

References

1. Abdul-Azim, M., Ehab, F.E. & Marwa, A.F. (2012). Development and validation of a reversed-phase column liquid chromatographic method for simultaneous determination of two novel gliptins in their binary mixtures with metformin. European Journal ofChem-istry, 3(2), 152-155. google scholar
2. Amit, C., & Bhuvnesh, K. S. (2021). Stability indicating RP-HPLC method for simultaneous determination of antidiabetic drugs, da-pagliflozin and saxagliptin. Journal of Advanced Scientific Re-search, 12(3), 67-75. google scholar
3. Anderson, R., Hayes, J., & Stephens, J.W. (2016). Pharmacokinetic, pharmacodynamic and clinical evaluation of saxagliptin in type 2 diabetes. Expert Opinion on Drug Metabolism and Toxicology, 12(4), 467-473. google scholar
4. Darshak, P., Ujashkumar, S., Jayvadan, P., Darshana, P., & Pa-van, P. (2021). A stability indicating RP-HPLC method valida-tion of simultaneous estimation of metformin HCl, dapagliflozin, saxagliptin in pharmaceutical dosage form. Journal of Pharma-ceutical Research International, 33(59A), 754-767. google scholar
5. Darshan, J. D. (2011). Saxagliptin: A dipeptidyl peptidase-4 Inhibitor in the treatment of type-2 diabetes mellitus. Jounal of Pharma-cology and Pharmacotherapeutics, 2(4), 230-235. google scholar
6. Faroqui, F.I., & Kakde, R.B. (2016). Reversed-phase Liquid chromatography with mass detection and characterisation of saxagliptin degradation related impurities. Journal of Chemical and Pharmaceutical Research, 8(7), 509-514. google scholar
7. Ghawate, V.B. & Chopade, B.L. (2019). Development and validation of RP-HPLC method for simultaneous estimation of dapagliflozin and saxagliptin in tablet dosage form. International Journal of Pharmacy and Pharmaceutical Research, 16(1), 189-199. google scholar
8. ICH, 2005. Q2 (R1), “Validation of analytical procedures: text and methodology”, ICH Harmonised Tripartite Guideline. Interna-tional Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Chicago, USA. Retrieved from https://database.ich.org/sites/default/files/ Q2%28R1%29%20Guideline.pdf google scholar

9. Kulsa, K., & Edelman, S. (2010). Saxagliptin: The evidence for its place in the treatment of type 2 diabetes mellitus. Core Evidence, 5, 23-27. google scholar
10. Lais, E.S., Ana, P.M. & Andrea, I.H.A Clarice, M.B.R.(2015).. Sta-bility indicating RP-LC-PDA method for quantitative analysis of saxagliptin in Pharmaceutical Dosage Form. Brazilian Journal of Pharmaceutical Sciences, 51, 461-466. google scholar
11. Maha, F.A.G., Omar, A.A., Miriam, F.A., & Mariam, M.T. (2015). Stability-indicating liquid chromatographic Method for determination of saxagliptin and Structure Elucidation of the major degra-dation products using LC-MS. Journal of Chromatographic Sci-ence, 53, 554-564. google scholar
12. Mahnoor, F. & Roshan, S. (2022). Analytical method Development and Validation for simultaneous estimation of Metformin and saxagliptin. International journal of pharmaceutical Science and research, 13, 2497-2507. google scholar
13. Mengistu, B., Ole, F.N., & Alemayehu, H. (2021). Cost-Effectiveness of Saxagliptin compared with Glibenclamide as a second-line ther-apy added to metformin for type-2 diabetes mellitus in Ethopia. MDM Policy & Practise, 6(1):23814683211005771. google scholar
14. Narender, B. & Shanmuga, P.P. (2021). Development and validation of RP-HPLC method for the simultaneous estimation of dapagliflozin and saxagliptin in bulk and pharmaceutical dosage forms. Inter-national Journal of Pharmaceutical Sciences and Research, 12, 314-320. google scholar
15. Padmaja, B. R., Sivagami, B., Chandrasekar, R., & Niranjan, B. M. (2018). A highly validated RP-HPLC method development for the simultaneous estimation of dapagliflozin and saxagliptin in tablet dosage forms. International Journal of Pharmaceutical Sciences and Drug Research, 10(5), 372-378. google scholar
16. Rageeb, Md., Usman, Md., Sufiyan, A., Chandrakanth, D., Tanvir, S., Bharat, J.& Imran, Md. (2020). Stability-Indicating RP-HPLC Method for determination of saxagliptin and dapagliflozin in bulk and tablet Dosage forms. Jounal of Pharmaceutical Sciences and Research, 12(4), 499-506. google scholar
17. Rahul, K.G., Ganesh, S.S., & Shraddha, J. (2019). Simultaneous esti-mation of dapagliflozin and saxagliptin in bulk drug and dosage form by RP-HPLC. Research Journal of Science and Technology, 11, 59-63. google scholar
18. Rohini, S., & Nagaraju, K. (2018). Analytical method development and validation for the estimation of saxagliptin and metformin by RP-HPLC method. International Journal of advance Research and Development, 3, 23-28. google scholar
19. Saiful, I.M., Taleb, H.M., Sukalyan, K.K., Abdul, H.M., & Rafiquz-zaman, M. Development and validation of RP-HPLC method for determination saxagliptin in bulk and dosage form. World Journal of Pharmacy and Pharmaceutical Sciences, 5, 107-119. google scholar
20. Sanchay, S. Z., Patel, S. G., Gaikwad, D. D., & Jadhav, S. L. (2019). Analytical Method Development of saxagliptin HCl by HPLC. Journal of Drug Delivery and Therapeutics, 9(4), 274-278. google scholar
21. Sarada, B., Narendra, K. R. K., & Pragati, K. B. (2017). Method development and validation of pioglitazone and saxagliptin by RP-HPLC. Indian Journal of Research in Pharmacy Biotechnology, 5(1), 44-46. google scholar
22. Singh, N., Bansal, P., Maithani, M., & Chauhan, Y. (2018). Develop-ment and validation of a stability- indicating RP-HPLC method for simultaneous determination of dapagliflozin and saxagliptin in fixed-dosage form. New Jounal of Chemistry, 42, 2459-2466. google scholar
23. Sridhar, L., Goutami, P., Vijay, D.D., Ramakrishna, K., Nageswara, R.R., & Prabhakar, S. (2014). LC-ESI-MS/MS Studies on Saxagliptin and its forced Degradation products, Analytical meth-ods, 6, 8212-8221. google scholar
24. Vijaya, U. B., Fainaz, M. C., Riya, B. G., & Tejaswini, R. K. (2018). Development and validation of analytical method for simultaneous estimation of saxagliptin and metformin HCL by using RP-HPLC method. International Research Journal of Pharmacy, 9(6), 22308407. google scholar
25. Vijaya, L.G., Narendra, D. (2020). Method development and validation for simultaneous estimation of dapagliflozin and saxagliptin by RP-HPLC method. World Journal of Pharmaceutical and Medical Research, 6(7), 243-248. google scholar