ENANTIOMETRIC SEPARATION OF SITAGLIPTIN IN A FIXED DOSE COMBINATION FORMULA OF SITAGLIPTIN AND METFORMIN BY A CHIRAL LIQUID CHROMATOGRAPHIC METHOD

  • Nagadeep Jaishetty Department of Chemistry, SRM University, Kattankulathur, Channai-603203, Tamilnadu., India
  • KAMARAJ PALANISAMY Department of Chemistry, SRM University, Kattankulathur, Channai-603203, Tamilnadu., India
  • ARTHANAREESWARI MARUTHAPILLAI Department of Chemistry, SRM University, Kattankulathur, Channai-603203, Tamilnadu., India

Abstract

Objective: Sitagliptin phosphate and metformin hydrochloride tablet is an FDA approved combination product for the treatment of diabetes mellitus type 2. There are no reported evidence for estimation of undesired (S)-sitagliptin in a combination product. The objective of this study was to develop a high sensitive liquid chromatography method for the determination of (S)-enantiomer of sitagliptin phosphate in a fixed dose combination formula of metformin and sitagliptin.


Methods: The proposed novel high-performance liquid chromatography (HPLC) method uses programmed gradient elution of a mixture of ethanol-diethylamine(DEA) 100:0.1 (v/v) as mobile phase-A and a mixture of methanol-water 60:40 (v/v) as mobile phase-B. The chromatographic conditions were designed to nullify the metformin interference and in which sitagliptin enantiomers elute first and followed by metformin. A satisfactory resolution (≥2.5) between (S)-sitagliptin and active form (R)-sitagliptin was achieved with gradient elution on Chiralpak IA column (5μm, 4 × 250 mm) at a flow rate of 0.5 ml/min and the detector wavelength set at 265 nm. The injection volume set as 10 µl. The developed method has been validated as per the International Conference on Harmonisation (ICH) guidelines.


Results: The proposed HPLC method for determination of (S)-sitagliptin, showed good linearity in the concentration range of 0.5 µg/ml to 13.6 µg/ml and capable to quantify accurately up to the lowest level (LOQ) of 0.017%. The validated method was successfully applied to quantify the (S)-sitagliptin for different marketed formulations of sitagliptin with metformin and sitagliptin alone, and the corresponding recovery values were found to be in the range of 95.1% to 98.4%.


Conclusion: The proposed validated HPLC method was found to be suitable for the quantitative determination of (S)-sitagliptin in the formulations of sitagliptin with metformin and sitagliptin alone.

Keywords: Sitagliptin phosphate, Metformin hydrochloride, Enantiomeric separation, Method development, Method validation

Downloads

Download data is not yet available.

Author Biography

Nagadeep Jaishetty, Department of Chemistry, SRM University, Kattankulathur, Channai-603203, Tamilnadu., India

Research scholor, Deparment of Chemistry

References

1. P K, R JR, Js K. A comparative study of efficacy and safety among metformin with sitagliptin, metformin with voglibose, and metformin with glimepiride in patients with type 2 diabetes mellitus. Asian J Pharm Clin Res 2017;10:313-6.
2. Singh RJ, Gupta AK, Kohli K. Diabetes mellitus: a review with edge of SGLT2 inhibitors. Int J Curr Pharm Sci 2018;10:1-2.
3. Souza Mello V, Gregorio BM, Cardoso-de-Lemos FS, de Carvalho L, Aguila MB, Mandarim-de-Lacerda CA. Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodeling in C57BL/6 mice fed on a very high-fat diet. Clin Sci 2010;119:239-50.
4. Beesley TE, Scott RP. Chiral chromatography. John Wiley and Sons; 1998.
5. Guideline IH. Specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substances. Q6A. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland; 1999.
6. Reddy BV, Raman N, Kumar BS, Rambabu C. Chiral separation of sitagliptin phosphate enantiomer by HPLC using amylose based chiral stationary phase. J Pharm Res 2013;7:546-50.
7. Ramesh T, Rao PN, Suresh K. Enantiomeric separation of sitagliptin by a validated chiral liquid chromatographic method. Anal Methods 2014;6:223-8.
8. Deepthi V, Poornima Y, Devala RG, Reddy ST. Stability indicating RP-HPLC method for analysis of sitagliptin in the bulk drug and its pharmaceutical dosage form. Int J Pharm Pharm Sci 2013;5:320-5.
9. Jeyabalan G, Nyola N. Analytical method development and validation of sitagliptin phosphate monohydrate in pure and tablet dosage form by derivative spectroscopy. J Appl Pharm Sci 2013;3:95.
10. Maste MM, Parate AN, Bhat AR. Validation and application of a high-performance liquid chromatography method for estimation of sitagliptin phosphate from bulk drug and pharmaceutical formulation. Asian J Res Chem 2011;4:1466-8.
11. Khan G, Sahu D, Agrawal YP, Sabarwal N, Jain A, Gupta AK. Simultaneous estimation of metformin and sitagliptin in tablet dosage form. Asian J Biochem Pharm Res 2011;1:352-8.
12. Raja T, Rao AL. Validated RP-HPLC method for simultaneous estimation of metformin hydrochloride and sitagliptin phosphate in bulk drug and pharmaceutical formulation. Int J Pharm Chem Biol Sci 2012:2:696-702.
13. Vasudevan M, Ravi J, Ravisankar S, Suresh B. ION-pair liquid chromatography technique for the estimation of metformin in its multicomponent dosage forms. J Pharm Biomed Anal 2001;25:77-84.
14. Malleswararao CS, Suryanarayana MV, Mukkanti K. Simultaneous determination of sitagliptin phosphate monohydrate and metformin hydrochloride in tablets by a validated UPLC method. Sci Pharm 2011;80:139-52.
15. El-Bagary RI, Elkady EF, Ayoub BM. Liquid chromatographic determination of sitagliptin either alone or in ternary mixture with metformin and sitagliptin degradation product. Talanta 2011;85:673-80.
16. Loni AB, Ghante MR, Sawant SD. Method development and validation for simultaneous determination of sitagliptin phosphate and metformin hydrochloride by RP-HPLC in bulk and tablet dosage form. Asian J Pharm Sci Res 2012;2:23-36.
17. Shyamala M, Mohideen S, Satyanarayana T, Narasimha Raju CH, Suresh Kumar P, Swetha K. Validated RP-HPLC for simultaneous estimation of sitagliptin phosphate and metformin hydrochloride in the tablet dosage form. Am J Pharm Tech Res 2011;1:193-201.
18. Peraman R, Gowra CS, Reddy YP, Peruru KK. Stability-indicating RP-HPLC method for simultaneous determination of metformin hydrochloride and sitagliptin phosphate in dosage forms. Chromatographia 2013;76:1153-62.
19. Nc K, Jk P. Method development and validation of a reversed-phase liquid chromatographic method for the simultaneous estimation of selected antidiabetic drugs in the presence of their degradation products. Asian J Pharm Clin Res 2018;11:345-52.
20. Trivedi A, Dixit N, Jhade DN. Modified quantification through high-performance liquid chromatography analysis for canagliflozin and metformin hydrochloride in bulk and tablets using eco-friendly green solvents. Int J Appl Pharm 2017;9:97-101.
21. Kulkarni AA, Vaidya IS. Flow injection analysis: an overview. J Crit Rev 2015;2:19-4.
22. Nagadeep J, Kamaraj P, Arthanareeswari M. Gradient RP-HPLC method for the determination of potential impurities in dabigatran etexilate in bulk drug and capsule formulations. Arabian J Chem 2015. https://doi.org/10.1016/j.arabjc.2015.09.006
23. Jaishetty N, Palanisamy K, Maruthapillai A, Jaishetty R. Trace level quantification of the (?) 2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1, 1, 1-trifluoro-3-butyn-2-ol genotoxic impurity in efavirenz drug substance and drug product using LC–MS/MS. Sci Pharm 2015;84:456-66.
24. Guideline IH. Impurities in new drug products Q3B (R2), Current Step; 2006. p. 4.
25. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use. Validation of Analytical Procedures; Text and Methodology ICH Q2 (R1); 2005.
26. Guideline IH. Good manufacturing practice guide for active pharmaceutical ingredients. Q7A, Current step; 2000. p. 4.
Statistics
362 Views | 184 Downloads
Citatons
How to Cite
Jaishetty, N., K. PALANISAMY, and A. MARUTHAPILLAI. “ENANTIOMETRIC SEPARATION OF SITAGLIPTIN IN A FIXED DOSE COMBINATION FORMULA OF SITAGLIPTIN AND METFORMIN BY A CHIRAL LIQUID CHROMATOGRAPHIC METHOD”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 11, no. 6, Apr. 2019, pp. 66-71, doi:10.22159/ijpps.2019v11i6.22699.
Section
Original Article(s)