Issue

Vol. 30 No. 8 (2018): Vol 30 Issue 8

Copyright (c) 2018 AJC

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

LC-MS Compatible Stability Indicating RP-UPLC Method for the Estimation of Ester Prodrug of Mycophenolic Acid in Injection Formulation

https://doi.org/10.14233/ajchem.2018.21445
G. Venkata Narasimha Rao1
1Formulations Research and Development Centre, Glenmark Pharmaceuticals Ltd., Taloja, Mumbai-410 208, India 2School of Biotechnology, VIGNAN University, Vadlamudi-522 213, India 3Department of Chemistry, GITAM University, Bengaluru-562 163, India *Corresponding author: E-mail: venkata.nr@gmail.com
Muralee Krishna1
1Formulations Research and Development Centre, Glenmark Pharmaceuticals Ltd., Taloja, Mumbai-410 208, India 2School of Biotechnology, VIGNAN University, Vadlamudi-522 213, India 3Department of Chemistry, GITAM University, Bengaluru-562 163, India *Corresponding author: E-mail: venkata.nr@gmail.com
Ravi Kumar Bellam2
1Formulations Research and Development Centre, Glenmark Pharmaceuticals Ltd., Taloja, Mumbai-410 208, India 2School of Biotechnology, VIGNAN University, Vadlamudi-522 213, India 3Department of Chemistry, GITAM University, Bengaluru-562 163, India *Corresponding author: E-mail: venkata.nr@gmail.com
R. Venkata Nadh3
1Formulations Research and Development Centre, Glenmark Pharmaceuticals Ltd., Taloja, Mumbai-410 208, India 2School of Biotechnology, VIGNAN University, Vadlamudi-522 213, India 3Department of Chemistry, GITAM University, Bengaluru-562 163, India *Corresponding author: E-mail: venkata.nr@gmail.com

Asian Journal of Chemistry, Vol. 30 No. 8 (2018): Vol 30 Issue 8

Abstract

This study explores the ultra performance liquid chromatography for the quantification of mycophenolate mofetil (an immunosuppressant agent) in an injection formulation. Mycophenolate mofetil was separated from its seven specified impurities on HSS (high strength silica) C18 column (100 × 2.1 mm, 1.8 μm). The optimized mobile phase is compatible to mass spectrometry and hence the method can be equally run on LC-MS system for mass determinations. Efficient UV detection at 250 nm enabled determination of mycophenolate mofetil with no interference from placebo solution, diluent and other specified and unspecified impurities. The retention time of mycophenolate mofetil in the method was 1.79 min and all other impurities were eluted within in 8 min. The method optimization studies show that the selectivity of mycophenolate mofetil and its impurities was dependent on the type of organic solvent and its elution strength. The method was validated for specificity, linearity, precision, accuracy and robustness in range of 50 to 150 % of target analyte concentration (i.e. 62.50-195.31 μg mL-1). The linearity of peak area responses versus concentrations was demonstrated by linear least square regression analysis. An excellent linear relation exists between the concentration and detector response (R2 > 0.9999). Precision of the test method was proved with a relative standard deviation less than 1.0 %.

Keywords

UPLC Mycophenolate mofetil Stability Indicating assay Validation.
Venkata Narasimha Rao1, G., Krishna1, M., Kumar Bellam2, R., & Venkata Nadh3, R. (2018). LC-MS Compatible Stability Indicating RP-UPLC Method for the Estimation of Ester Prodrug of Mycophenolic Acid in Injection Formulation. Asian Journal of Chemistry, 30(8), 1915–1924. https://doi.org/10.14233/ajchem.2018.21445
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. K.P. Platz, H.W. Sollinger, D.A. Hullett, D.E. Eckhoff, E.M. Eugui and A.C. Allison, Transplantation, 51, 27 (1991); https://doi.org/10.1097/00007890-199101000-00003.
  2. E.M. Eugui, S.J. Almquist, C.D. Muller and A.C. Allison, Scand. J. Immunol., 33, 161 (1991); https://doi.org/10.1111/j.1365-3083.1991.tb03746.x.
  3. T.R. Srinivas, J.D. Schold, G. Guerra, A. Eagan, C.M. Bucci and H.U. MeierKriesche, Am. J. Transplant., 7, 586 (2007); https://doi.org/10.1111/j.1600-6143.2006.01658.x.
  4. S.M. Flechner, L. Zhou, I. Derweesh, B. Mastroianni, K. Savas, D. Goldfarb, C.S. Modlin, V. Krishnamurthi and A. Novick, Transplantation, 76, 1729 (2003); https://doi.org/10.1097/01.TP.0000093502.26208.42.
  5. Drug bank, Mycophenolate Mofetil; https://www.drugbank.ca/drugs/DB00688.
  6. National Library of Medicine, USA, extracted from ChemIDplus, UNII: 9242ECW6R0; https://chem.nlm.nih.gov/chemidplus/rn/128794-94-5.
  7. Mycophenolate Mofetil Monograph; United States Pharmacopoeia; USP40 NF35; 2017; p. 5247 (2017).
  8. P.W. Brian and H.G. Hemming, Microbiology, 1, 158 (1947).
  9. P.W. Clutterbuck, A.E. Oxford, H. Raistrick and G. Smith, Biochem. J., 26, 1441 (1932); https://doi.org/10.1042/bj0261441.
  10. J.H. Birkinshaw and M.S. Samant, Biochem. J., 74, 369 (1960); https://doi.org/10.1042/bj0740369.
  11. W. Harrison, H.M. Shearer and J. Trotter, J. Chem. Soc., Perkin Trans. 2, 1542 (1972); https://doi.org/10.1039/p29720001542.
  12. Mycophenolate Mofetil Injection, USP40-NF35, The United States Pharmacopoeia Convention, Inc., Rockville, MD, p. 5250 (2017).
  13. Mycophenolate Mofetil Tablet, USP40-NF35, The United States Pharmacopoeia Convention, Inc., Rockville, MD, p. 5253 (2017).
  14. Mycophenolate Mofetil Capsule, USP40-NF35, The United States Pharmacopoeia Convention, Inc., Rockville, MD, p. 5248 (2017).
  15. Mycophenolate Mofetil for Oral Suspension, USP40-NF35, The United States Pharmacopoeia Convention, Inc., Rockville, MD, p. 5253 (2017).
  16. Mycophenolate Mofetil Monograph; European Pharmacopoeia, European Directorate for the Quality of Medicine & Health Care of the Council of Europe (EDQM), edn 9, vol. 3, pp. 3104-3105 (2016).
  17. Mycophenolate Mofetil; Mycophenolate Capsules Monograph, Indian Pharmacopoeia, pp. 2268-2270 (2014).
  18. I. Tsina, M. Kaloostian, R. Lee, T. Tarnowski and B. Wong, J. Chromatogr. B Biomed. Sci. Appl., 681, 347 (1996); https://doi.org/10.1016/0378-4347(96)00038-2.
  19. A.L. Rao, P.V. Srinivas and J.V. Rao, Asian J. Pharm. Res. Health Care, 2, 266 (2010).
  20. P.R. Abhilash, K.V. Kumar and V.S. Kumar, Br. J. Pharm. Res., 3, 363 (2013); https://doi.org/10.9734/BJPR/2013/2286.
  21. T.V. Reddy, G. Ramu and C. Rambabu, Anal. Chem.: An Indian J., 12, 156 (2013).
  22. V.P. Choudhari and A.P. Nikalje, Adv. Chem., Article ID 719385 (2014); https://doi.org/10.1155/2014/719385.
  23. M. Bolon, L. Jeanpierre, M. El Barkil, K. Chelbi, M. Sauviat and R. Boulieu, J. Pharm. Biomed. Anal., 36, 649 (2004); https://doi.org/10.1016/j.jpba.2004.07.034.
  24. M. Shipkova, P.D. Niedmann, V.W. Armstrong, E. Schütz, E. Wieland, L.M. Shaw and M. Oellerich, Clin. Chem., 44, 1481 (1998).
  25. D. Teshima, K. Otsubo, N. Kitagawa, S. Yoshimura, Y. Itoh and R. Oishi, J. Clin. Pharm. Ther., 28, 17 (2003); https://doi.org/10.1046/j.1365-2710.2003.00450.x.
  26. C.G. Patel, A.E. Mendonza, F. Akhlaghi, O. Majid, A.K. Trull, T. Lee and D.W. Holt, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 813, 287 (2004); https://doi.org/10.1016/j.jchromb.2004.10.004.
  27. D.G. Watson, F.G. Araya, P.J. Galloway and T.J. Beattie, J. Pharm. Biomed. Anal., 35, 87 (2004); https://doi.org/10.1016/j.jpba.2003.12.011.
  28. M.A. Barzoki, M. Rouini, K. Gholami, M. Lessan-Pezeshki and S. Rezaee, Daru, 13, 120 (2005).
  29. G. Khoschsorur and W. Erwa, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 799, 355 (2004); https://doi.org/10.1016/j.jchromb.2003.10.074.
  30. D.V. McCalley and R.G. Brereton, J. Chromatogr. A, 828, 407 (1998); https://doi.org/10.1016/S0021-9673(98)00590-1.
  31. W.R. Melander, J. Stovekeen and C. Horvàth, J. Chromatogr. A, 185, 111 (1979); https://doi.org/10.1016/S0021-9673(00)85601-0.
  32. The United States Pharmacopoeia 40 National Formulary 35, Description and Solubility (5.30); General Notices; The United States Pharmacopoeia Convention, Inc., Rockville, MD (2017).
  33. J.J. Kirkland, M.A. Van Straten and H.A. Claessens, J. Chromatogr. A, 691, 3 (1995); https://doi.org/10.1016/0021-9673(94)00631-I.
  34. L.R. Snyder, J.J. Kirkland and J.L. Glajch, Practical HPLC Method Development, John Wiley & Sons (2012).
  35. R.M. Kennedy, Methods Enzymol., 182, 339 (1990); https://doi.org/10.1016/0076-6879(90)82029-2.
  36. HSS C18; Waters catalogue, Waters Acquity UPLC HSS Columns, Retrieved from.
  37. https://www.waters.com/webassets/cms/support/docs/715001429.pdf.
  38. H. Colin and G. Guiochon, J. Chromatogr. A, 141, 289 (1977); https://doi.org/10.1016/S0021-9673(00)93537-4.
  39. H. Engelhardt and G. Ahr, Chromatographia, 14, 227 (1981); https://doi.org/10.1007/BF02260156.
Read More
Author biographies is not available.
Download
PDF
Statistic
Read Counter : 1 Download : 2