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Evaluation of Process Impurities and Degradants of Sitagliptin Phosphate by Validated Stability Indicating RP-LC Method
Corresponding Author(s) : Nagi Reddy Vuyyuru
Asian Journal of Chemistry,
Vol. 29 No. 9 (2017): Vol 29 Issue 9
Abstract
A new stability-indicating high-performance liquid chromatographic method has been developed for evaluation of degradants, starting materials and process related impurities during the synthesis of sitagliptin phosphate (SIT-P). Separations were achieved on a RP C18 column with linear gradient elution of 0.02 M phosphate buffer at pH 7 and acetonitrile as mobile phase constituents. The flow rate was 1 mL/min and photodiode array detector wavelength was set at 210 nm. Method development was carried in order to elute all starting materials, intermediates during reaction monitoring of stage wise synthesis. Sitagliptin phosphate was subjected for stress conditions like acidic and basic hydrolysis, oxidative, photolytic, neutral and thermal degradation and > 95 % mass balance was achieved, thus ensuring stability indicating capability of the method. Major degradants raised due to acid and base stress were studied by LCMS, identified as Imp-1 (m/z 193.0) and Imp-4 (m/z 234.20), synthesized and subsequently validated along with all other process related impurities as per ICH with respect to specificity, precision, linearity, LOD, LOQ, accuracy, ruggedness and robustness.
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- Drugs.com, Overview of Sitagliptin https://www.drugs.com/cdi/sitagliptin.html.
- RxList The Internet Drug Index, Drug Description of Januvia Tablet, http://www.rxlist.com/januvia-drug.htm.
- D.P. Sonune and M.K. Mone, Int. J. Pharm. Sci. Res., 4, 3494 (2013); https://doi.org/10.13040/IJPSR.0975-8232.4(9).3494-03.
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- T. Sohajda, W.H. Hu, L.L. Zeng, H. Li, L. Szente, B. Noszál and S. Béni, Electrophoresis, 32, 2648 (2011); https://doi.org/10.1002/elps.201000639.
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- B.G. Chaudhari, N.M. Patel and P.B. Shah, J. AOAC Int., 90, 1242 (2007).
- United States Pharmacopeia, 39-NF-34 ed., Rockville, MD: The United States Pharmacopeial Convention.
- ICH, Validation of Analytical Procedures: Text and Methodology (Q2(R1)): International Conference on Harmonization; Geneva: IFPMA (2005).
- ICH, Stability Testing of New Drug Substances and Products (Q1A(R2)): International Conference on Harmonization; Geneva: IFPMA (2003).
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References
Drugs.com, Overview of Sitagliptin https://www.drugs.com/cdi/sitagliptin.html.
RxList The Internet Drug Index, Drug Description of Januvia Tablet, http://www.rxlist.com/januvia-drug.htm.
D.P. Sonune and M.K. Mone, Int. J. Pharm. Sci. Res., 4, 3494 (2013); https://doi.org/10.13040/IJPSR.0975-8232.4(9).3494-03.
M. Fistikci, O. Gundogdu, D. Aktas, H. Secen, M.F. Sahin, R. Altundas and Y. Kara, Tetrahedron, 68, 2607 (2012); https://doi.org/10.1016/j.tet.2012.01.095.
P. Ramalingam, V. Udaya Bhaskar, Y. Padmanabha Reddy and K. Vinod Kumar, Indian J. Pharm. Sci., 76, 407 (2014); https://doi.org/10.4103/0250-474X.143080.
C.S.N. Malleswararao, M.V. Suryanarayana and K. Mukkanti, Sci. Pharm., 80, 139 (2012); https://doi.org/10.3797/scipharm.1110-13.
J.G. Swales, R.T. Gallagher, M. Denn and R.M. Peter, J. Pharm. Biomed. Anal., 55, 544 (2011); https://doi.org/10.1016/j.jpba.2011.02.030.
T. Sohajda, W.H. Hu, L.L. Zeng, H. Li, L. Szente, B. Noszál and S. Béni, Electrophoresis, 32, 2648 (2011); https://doi.org/10.1002/elps.201000639.
W. Zeng, D.G. Musson, A.L. Fisher, L. Chen, M.S. Schwartz, E.J. Woolf and A.Q. Wang, J. Pharm. Biomed. Anal., 46, 534 (2008); https://doi.org/10.1016/j.jpba.2007.11.003.
B.G. Chaudhari, N.M. Patel and P.B. Shah, J. AOAC Int., 90, 1242 (2007).
United States Pharmacopeia, 39-NF-34 ed., Rockville, MD: The United States Pharmacopeial Convention.
ICH, Validation of Analytical Procedures: Text and Methodology (Q2(R1)): International Conference on Harmonization; Geneva: IFPMA (2005).
ICH, Stability Testing of New Drug Substances and Products (Q1A(R2)): International Conference on Harmonization; Geneva: IFPMA (2003).
ICH, Stability Testing: Photostability Testing of New Drug Substances and Products (Q1B): International Conference on Harmonization; Geneva: IFPMA (1996).