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Vol. 37 No. 2 (2025): Vol 37 Issue 2, 2025

Copyright (c) 2025 Nishant Goswami, Dr. Mudhulkar Raju

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Quality by Design and Green Chemistry Analytical Method: New Combined Methodology for Quantification of Cyanocobalamin and Benzyl Alcohol in Parenteral Formulations

https://doi.org/10.14233/ajchem.2025.32978
Nishant Goswami
Department of Chemistry, Koneru Lakshmaiah Education Foundation, Bowrampet, Hyderabad-500043, India
https://orcid.org/0009-0002-3752-9293
Mudhulkar Raju
Department of Chemistry, Koneru Lakshmaiah Education Foundation, Bowrampet, Hyderabad-500043, India
https://orcid.org/0000-0002-4586-8749

Corresponding Author(s) : Mudhulkar Raju

m.raju@klh.edu.in

Asian Journal of Chemistry, Vol. 37 No. 2 (2025): Vol 37 Issue 2, 2025

Abstract

Developing methods for the analysis of hazardous chemicals and complex parenteral formulations is a challenging process. To address these challenges, the integration of green chemistry principles and design of experiments proves highly effective. This study introduces a novel approach that combines green analytical chemistry and design of experiments (DoE) to develop a sensitive, reproducible and stability indicating method by high-pressure liquid chromatography method for quantification of cyanocobalamin and benzyl alcohol in liquid parenteral formulations. A high-pressure liquid chromatography methodology for quantification of cyanocobalamin and benzyl alcohol was established with an analytical quality by design principle. The method employs the central composite response, which optimizes the connection between factors and responses with reduced number of design points and experimental runs, yielding statistically significant results and enhancing analytical quality. Separation of cyanocobalamin and benzyl alcohol was achieved on Zorbax C-8 column (250 * 4.6 mm with 5 µm) using buffer as ammonium formate (pH 2.5) and acetonitrile with a gradient mobile phase at a pump flow of 1.0 mL/min. Detection was performed by ultra violet detector set to a wavelength of 254 nm. The proposed method is validated in line with ICH Q2 (R2) guidelines, evaluating parameters such as linearity, accuracy, precision, system suitability, sensitivity, robustness and solution stability, all within acceptable ranges. The eco-affability and greenness of new developed method were checked by using the Analytical Greenness metric, Green Analytical Procedure Index and National Environmental Method Index, confirming its suitability as an environmentally sustainable analytical approach.

Keywords

Cyanocobalamin Benzyl alcohol RP-HPLC Analytical quality by design Green analytical chemistry
Goswami, N., & Raju, M. (2025). Quality by Design and Green Chemistry Analytical Method: New Combined Methodology for Quantification of Cyanocobalamin and Benzyl Alcohol in Parenteral Formulations. Asian Journal of Chemistry, 37(2), 291–299. https://doi.org/10.14233/ajchem.2025.32978
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References
  1. S. Mitra, S. Paul, S. Roy, H. Sutradhar, T.B. Emran, M.U. Khandaker, F. Nainu, M. Almalki, P. Wilairatana and M.S. Mubarak, Molecules, 27, 555 (2022); https://doi.org/10.3390/molecules27020555
  2. E. Tourkochristou, C. Triantos and A. Mouzaki, Front. Immunol., 12, 665968 (2021); https://doi.org/10.3389/fimmu.2021.665968
  3. I. Ortigues-Marty, D. Micol, S. Prache, D. Dozias and C.L. Girard, Reprod. Nutr. Dev., 45, 453 (2005); https://doi.org/10.1051/rnd:2005038
  4. W. Elfalleh, N. Nasri, N. Marzougui, I. Thabti, A. M’rabet, Y. Yahya, B. Lachiheb, F. Guasmi and A. Ferchichi, Int. J. Food Sci. Nutr., 60(S2), 197 (2009); https://doi.org/10.1080/09637480903067037
  5. J.B. Kirkland, Curr. Pharm. Design, 15, 3 (2009); https://doi.org/10.2174/138161209787185823
  6. D. Guggisberg, M.C. Risse and R. Hadorn, Meat Sci., 90, 279 (2012); https://doi.org/10.1016/j.meatsci.2011.07.009
  7. L. Ibrahim and A. Usman, Turk. J. Chem., 46, 320 (2021); https://doi.org/10.55730/1300-0527.3309
  8. J.T. Polaski, S.M. Webster, J.E. Johnson Jr. and R.T. Batey, J. Biol. Chem., 292, 11650 (2017); https://doi.org/10.1074/jbc.M117.787176
  9. Ž.T. Rakuša, R. Roškar, N. Hickey and S. Geremia, Molecules, 28, 240 (2023); https://doi.org/10.3390/molecules28010240
  10. D.E. Sherbiny and M.E.K. Wahba, J. Taibah Univ. Sci., 14, 294 (2019); https://doi.org/10.1080/16583655.2020.1736768
  11. L. Stroppel, T. Schultz-Fademrecht, M. Cebulla, R.J. Marhöfer, P.M. Selzer, M. Blech and P. Garidel, Pharmaceutics, 15, 563 (2023); https://doi.org/doi:10.3390/pharmaceutics15020563
  12. M. Kester and K.D. Karpa and K.E. Vrana, Elsevier’s Integrated Review Pharmacology Book, Elsevier, edn. 2, pp. 41-78 (2012).
  13. K.M. Khan, A.R. Khan, S. Perveen, Zia-Ullah, N. Ambreen and W. Voelter, Open Anal. Chem. J., 2, 74 (2008); https://doi.org/10.2174/1874065000802010074
  14. B.J. Floor, A.E. Klein, N. Muhammad and D. Ross, J. Pharm. Sci., 74, 197 (1985); https://doi.org/10.1002/jps.2600740219
  15. G.C. Wood, M.R. Iyer, A.M. Geller, A.M. Fleischner and B.B. Sheth, J. Liq. Chromatogr. Relat. Technol., 21, 2183 (1998); https://doi.org/10.1080/10826079808006617
  16. M.M. Baker, D.S. El-Kafrawy, M.M. Abdel-Khalek and T.S. Belal, Chromatographia, 83, 191 (2020); https://doi.org/10.1007/s10337-019-03832-8
  17. ICH Q2(R2) guideline on validation of analytical procedures - 2022.
  18. P. Anastas and N. Eghbali, Chem. Soc. Rev., 39, 301 (2010); https://doi.org/10.1039/B918763B
  19. S.K. Muchakayala, N.K. Katari, T. Dongala, V.M. Marisetti, G. Vyas and R.V.K. Vegesna, J. Iran. Chem. Soc., 19, 1397 (2022); https://doi.org/10.1007/s13738-021-02388-5
  20. L.P. Kowtharapu, N.K. Katari, S. Ch, C.A. Sandoval, S.K. Muchakayala and N. Konduru, Biomed. Chromatogr., 36, e5359 (2022); https://doi.org/10.1002/bmc.5359
  21. J. Plotka-Wasylka, Talanta, 181, 204 (2018); https://doi.org/10.1016/j.talanta.2018.01.013
  22. D. Mohamed and M.M. Fouad, Microchem. J., 157, 104873 (2020); https://doi.org/10.1016/j.microc.2020.104873
  23. A. Galuszka, Z.M. Migaszewski, P. Konieczka and J. Namieœnik, Trends Analyt. Chem., 37, 61 (2012); https://doi.org/10.1016/j.trac.2012.03.013
  24. L.P. Kowtharapu, N.K. Katari, C.A. Sandoval, S.K. Muchakayala and V.K. Rekulapally, J. Sep. Sci., 45, 1711 (2022); https://doi.org/10.1002/jssc.202100979
  25. M. Sajid and J. Plotka-Wasylka, Talanta, 238, 123046 (2022); https://doi.org/10.1016/j.talanta.2021.123046
  26. F. Pena-Pereira, W. Wojnowski and M. Tobiszewski, Anal. Chem., 92, 10076 (2020); https://doi.org/10.1021/acs.analchem.0c01887
  27. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human use ich Harmonised Guideline, Analytical Procedure Development q14 (2022).
  28. S.K. Muchakayala, K. Pavithra, N.K. Katari, V.M. Marisetti, T. Dongala and R.V.K. Vegesna, Anal. Methods, 13, 3705 (2021); https://doi.org/10.1039/D1AY01096D
  29. I. Radic, M. Runje and S. Babic, J. Pharm. Biomed. Anal., 201, 114091 (2021); https://doi.org/10.1016/j.jpba.2021.114091
  30. L.P. Kowtharapu, N.K. Katari, C.A. Sandoval, S.K. Muchakayala and V.K. Rekulapally, J. AOAC Int., 105, 1247 (2022); https://doi.org/10.1093/jaoacint/qsac072
  31. R. Deidda, S. Orlandini, P. Hubert and C. Hubert, J. Pharm. Biomed. Anal., 161, 110 (2018); https://doi.org/10.1016/j.jpba.2018.07.050
  32. P. Jackson, P. Borman, C. Campa, M. Chatfield, M. Godfrey, P. Hamilton, W. Hoyer, F. Norelli, R. Orr and T. Schofield, Anal. Chem., 91, 2577 (2019); https://doi.org/10.1021/acs.analchem.8b04596
  33. A.H. Schmidt and I. Molnár, J. Pharm. Biomed. Anal., 78-79, 65 (2013); https://doi.org/10.1016/j.jpba.2013.01.032
  34. H.K. Chanduluru and A. Sugumaran, RSC Adv., 11, 27820 (2021); https://doi.org/10.1039/D1RA04843K
  35. V.M. Marisetti, P. Katakam, V.K. Siddhani and N.K. Katari, Biomed. Chromatogr., 35, e5194 (2021); https://doi.org/10.1002/bmc.5194
  36. K. Alfonsi, J. Colberg, P.J. Dunn, T. Fevig, S. Jennings, T.A. Johnson, H.P. Kleine, C. Knight, M.A. Nagy, D.A. Perry and M. Stefaniak, Green Chem., 10, 31 (2008); https://doi.org/10.1039/B711717E
  37. D. Prat, A. Wells, J. Hayler, H. Sneddon, C.R. McElroy, S. Abou-Shehada and P.J. Dunn, Green Chem., 18, 288 (2016); https://doi.org/10.1039/C5GC01008J
  38. M. Tobiszewski, S. Tsakovski, V. Simeonov, J. Namieœnik and F. Pena-Pereira, Green Chem., 17, 4773 (2015); https://doi.org/10.1039/C5GC01615K
  39. C. Capello, U. Fischer and K. Hungerbühler, Green Chem., 9, 927 (2007); https://doi.org/10.1039/b617536h
  40. M. Tobiszewski and J. Namieœnik, Ecotoxicol. Environ. Saf., 120, 169 (2015); https://doi.org/10.1016/j.ecoenv.2015.05.043
  41. A. Galuszka, Z. Migaszewski and J. Namiesnik, Trends Analyt. Chem., 50, 78 (2013); https://doi.org/10.1016/j.trac.2013.04.010
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