SIMULTANEOUS DETERMINATION OF METFORMIN, LINAGLIPTIN IN JENTADUETO AND METFORMIN, SAXAGLIPTIN IN KOMBIGLYZE BY LC-MS METHOD
Objective: The objective of the present investigation was to develop a novel, simple and economic method for the determination of metformin (MET), linagliptin (LIN) and saxagliptin (SAX) in jentadueto and kombiglyze sample by employing the liquid chromatography and mass spectrometric method for estimation in bulk and pharmaceutical dosage form in presence of degradation products.
Methods: The chromatographic separation was achieved by using the mobile phase composition of methanol and ammonium acetate buffer pH 4.5 (85:15 % v/v) on the Hypurity advance C-18 column at a flow rate of 0.5 ml/min. Ion signals m/z â€œ130.10/70.10, 473.10/420.40 and 316.30/180.20â€ for metformin, linagliptin and saxagliptin respectively measured in positive ion mode. The detailed validation of the method was performed as per ICH guidelines.
Results: The results of all validation parameters found within acceptance limits. The linearity of the drugs was found to be in the concentration range of 50â€“5000 ng/ml for all the drugs. Accuracy of the drugs was found to be from 94-102% and precision was found 4.67% RSD for all three drugs. The validated method was employed for the determination of drugs in the formulation and also determined the drugs in the presence of degradation products under stress conditions.
Conclusion: The method was developed and validated as per guidelines. Hence, this method can be used for the simultaneous determination of metformin, linagliptin and metformin, saxagliptin in bulk and combined dosage forms.
2. Moses R. Fixed combination of repaglinide and metformin in the management of type 2 diabetes. Diabetes Metab Syndr Obes: Targets Ther 2009;2:101-9.
3. Tripathi KD. Essential of medical pharmacology. 5th Ed. Jaypee Brothers Medical publisher, New Delhi; 2004. p. 248â€“9.
4. Kirby M, Yu DM, O'Connor S, Gorrell MD. Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition. Clin Sci 2009;118:31â€“41.
5. Salsali A, Pratley RE. Does addition of sitagliptin to metformin monotherapy improve glycemic control in patients with type 2 diabetes mellitus? Nat Clin Pract Endocrinol Metab 2007;3:450â€“1.
6. Augeri DJ, Robl JA, Betebenner DA, Magnin DR, Khanna A, Robertson JG, et al. Discovery and preclinical profile of saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005;48:5025-37.
7. Kulasa K, Edelman S. Saxagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus. Core Evidence 2010;5:23-37.
8. Parag P, Imran M, Bairagi V, Ahire Y. Development and validation of stability indicating UV spectrophotometric method for the estimation of sitagliptin phosphate in bulk and tablet dosage form. J Pharm Res 2011;4(Suppl 3):871-3.
9. Khan, Agrawal YP, Sabarwal N, Jain A, Gupta AK. Simultaneous estimation of metformin and sitagliptin in tablet dosage form. Asian J Biochem Pharma Res 2011;1(Suppl 2):352-8.
10. Ramzia El-Bagary, Ehab EF, Bassam AM. Spectrofluorometric and Spectrophotometric methods for the determination of sitagliptin in binary mixture with metformin and ternary mixture with metformin and sitagliptin alkaline degradation product. Int J Biomed Sci 2011;7(Suppl 1):62-9.
11. Ravi PP, Sastry BS, Rajendra PY, Appala RN. Simultaneous estimation of metformin HCl and sitagliptin phosphate in tablet dosage forms by RP-HPLC. Res J Pharm Tech 2011;4(Suppl 4):646-9.
12. Shyamala M, Mohideen S, Satyanarayana T, Narasimha R, Suresh K, Swetha K. Validated RP-HPLC for simultaneous estimation of sitagliptin phosphate and metformin hydrochloride in tablet dosage form. Am J Pharm Tech Res 2011;1(Suppl 2):93-101.
13. Zeng W, Xu Y, Constanzer M, Woolf EJ. Determination of sitagliptin in human plasma using protein precipitation and tandem mass spectrometry. J Chromatogr Biomed Appl 2010;878(Suppl 21):1817-23.
14. Zeng W, Musson DG, Fisher AL, Chen L, Schwartz MS, Woolf EJ, et al. Determination of sitagliptin in human urine and hemodialysate using turbulent flow online extraction and tandem mass spectrometry. J Pharm Biomed Anal 2008;46(Suppl 3):534-42.
15. Nirogi R, Kandikere V, Mudigonda K, Komarneni P, Aleti R, Boggavarapu R. Sensitive liquid chromatography-tandem mass spectrometry method for the quantification of sitagliptin, a DPP-4 inhibitor, in human plasma using liquid-liquid extraction. Biomed Chromatography 2008;22(Suppl 2):214â€“22.
16. Ucakturk, Ebru. Development of a gas chromatography-mass spectrometry method for the analysis of sitagliptin in human urine. J Pharm Biomed Anal 2013;74:71-6.
17. Haak T. Combination of linagliptin and metformin for the treatment of patients with type 2 diabetes. Clin Med Insights Endocrinol Diabetes 2015;8:1-6.
18. Madhukar A, Prince, Vijay Kumar R, Sanjeev Y, Jagadeeshwar K, Raghupratap. Simple and sensitive analytical method development and validation of metformin hydrochloride by RP-HPLC. Int J Pharm Pharm Sci 2011;3(Suppl 3):117-20.
19. Nazar Mustafa Mansoory, Anurekha Jain. Simultaneous estimation of metformin hydrochloride, pioglitazone hydrochloride and gliclazide by a validated RP-HPLC method in the solid dosage form. Int J Pharm Sci 2012;4(Suppl 5):72-6.
20. Bonde S, Bhadane RP, Avinash Gaikwad, Deepak Katale, Sumit Gavali S Narendiran. A simple and sensitive method for determination of Metformin and Sitagliptin in human plasma using liquid chromatography and tandem mass spectrometry. Int J Pharm Pharm Sci 2013;5(Suppl3):463-70.
21. Anushaakula N, Prajwala, Sandhya M, Uma Maheswara Rao. Development and validation of an RP-HPLC method for simultaneous estimation of metformin hydrochloride and gliclazide in bulk and combined dosage form. Int J Pharm Sci 2013;5(Suppl 4):511-7.
22. Janardhan Swamy A, Harinadha Baba K. Analytical method development and method validation for the simultaneous estimation of metformin HCl and linagliptin in bulk and tablet dosage form by RP-HPLC method. Int J Pharm 2013;3(Suppl 3):594-600.
23. James D Terish Bino, Kannappan, Sasi Jith, Suresh Kumar. Simultaneous estimation and method development for l-carnitine and metformin in human plasma using the liquid chromatography-mass spectrometer. Asian J Pharm Clin Res 2015;8:185-91.
24. ICH Tripartite Guideline. Validation of analytical procedures: text and methodology. International Conference on Harmonization, European Commission, Japan and USA; 2005.
25. Radhika Shah, Ragin Shah. Stability indicating RP-HPLC method for simultaneous estimation of dosulepin hydrochloride and methylcobalamin in tablet dosage form. Int J Appl Pharm 2017;9:69-75.
26. Sridhar Siddiraju, Rayala Kavitha, Muvvala Sudhakar. Reverse phase high-performance liquid chromatography method development and validation for the simultaneous estimation of gatifloxacin and flurbiprofen in the pharmaceutical dosage form. Asian J Pharm Clin Res 2015;8:242-2.
27. Kavitha KY, Geetha G, Hariprasad R, Kaviarasu M, Venkatnarayanan R. Development and validation of stability indicating an RP-HPLC method for the simultaneous estimation of linagliptin and metformin in the pure and pharmaceutical dosage form. J Chem Pharm Res 2013;5:230-5.
28. Asiya Begum, Shilpa K, A Ajitha, V Uma Maheshwar Rao. Development and validation of stability indicating a Rp-HPLC method for saxagliptin and metformin in tablet dosage form. Int J Pharm 2014;4:271-9.