Issue

Vol. 36 No. 10 (2024): Vol 36 Issue 10, 2024

Copyright (c) 2024 Sreenivasa Rao Battula, RAJESH VARMA B, Pavani P, VENKATA SWAMY T, Rekha k

Creative Commons License

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

Characterization of Pimavanserin Stress Degradation Products by LCMS/MS and Optimization of Green Analytical HPLC Method for Quantification of Pimavanserin and its Impurities

https://doi.org/10.14233/ajchem.2024.32475
B. Rajesh Varma
Department of Chemistry, GITAM Institute of Science, GITAM (Deemed to be University), Visakhapatnam-530045, India
https://orcid.org/0000-0001-8580-8575
P. Pavani
Department of Chemistry, Prasad V. Potluri Siddhartha Institute of Technology, Kanuru, Vijayawada-520007, India
https://orcid.org/0000-0003-0712-8907
T. Venkata Swamy
Department of Chemistry, Tagore Government Arts and Science College (Affiliated to Pondicherry University), Puducherry-605008, India
https://orcid.org/0000-0001-8969-6806
K. Rekha
Department of Biotechnology, Dr. V.S. Krishna Government Degree College, Visakhapatnam-530022, India
https://orcid.org/0009-0008-3233-3578
B. Sreenivasa Rao
Department of Chemistry, GITAM Institute of Science, GITAM (Deemed to be University), Visakhapatnam-530045, India
https://orcid.org/0000-0002-0242-5032

Corresponding Author(s) : B. Sreenivasa Rao

sbattula2@gitam.edu

Asian Journal of Chemistry, Vol. 36 No. 10 (2024): Vol 36 Issue 10, 2024

Abstract

Green HPLC analytical procedures can quantify contaminants since they employ few hazardous chemicals and waste, reducing environmental impact and improving laboratory safety. In literature, no green analytical method reported for quantification of impurities in pimavanserin and hence this study aimed to establish green analytical method. The method comprises XBridge BEH C18 3.0 µm (100 mm × 4.6 mm) C18 column along with ethanol and 0.01 M aqueous orthophosphoric acid in 60:40 (v/v) at 0.75 mL/min flow and 249 nm wavelength. These conditions proved to be appropriate for asymmetric peak shape along with good resolution and permissible tailing. This method produces well correlated linearity in 3-18 µg/mL for pimavanserin and 0.03-0.18 µg/mL for impurities. This method exhibit a very sensitive detection limit of 0.01 µg/mL that enables precise and accurate impurity quantification at very low concentrations. All validation parameters performed and permissible results observed for both pimavanserin and impurities. Different stress conditions like acid, base, oxidative, thermal and photolytic was analyzed for pimavanserin to evaluate method effectiveness to resolve stress degradation products (DPs). The stress study identifies two distinct DPs in acid and base degradation chromatograms and was named as DP 1 and DP 2. The applicability of MSn studies and mass fragmentation confirms DP 1 as (4-fluorobenzyl)(1-methylpiperidin-4-yl)carbamic acid and DP 2 as [4-(2-methylpropoxy)benzyl]carbamic acid. The GAPI (Green Analytical Procedure Index) and AGREE (Analytical GREEnness) metric tools were employed to assess the method greenness. This proposed green method can significantly reduce the usage of hazardous solvents without losing chromatographic performance and method efficiency. This study concluded that the method is suitable for quantifying pimavanserin and its impurities along with identification of degradation products.

Keywords

Pimavanserin Green analytical method GAPI AGREE Degradation products
Varma, B. R., Pavani, P., Swamy, T. V., Rekha, K., & Rao, B. S. (2024). Characterization of Pimavanserin Stress Degradation Products by LCMS/MS and Optimization of Green Analytical HPLC Method for Quantification of Pimavanserin and its Impurities. Asian Journal of Chemistry, 36(10), 2452–2460. https://doi.org/10.14233/ajchem.2024.32475
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. J.H. Friedman, Expert Opin. Pharmacother., 14, 1969 (2013); https://doi.org/10.1517/14656566.2013.819345
  2. I. Yunusa, M.L. El Helou and S. Alsahali, Front. Pharmacol., 11, 87 (2020); https://doi.org/10.3389/fphar.2020.00087
  3. L.R. Gardell, K.E. Vanover, L. Pounds, R.W. Johnson, R. Barido, G.T. Anderson, I. Veinbergs, A. Dyssegaard, P. Brunmark, A. Tabatabaei, R.E. Davis, M.R. Brann, U. Hacksell and D.W. Bonhaus, J. Pharmacol. Exp. Ther., 322, 862 (2007); https://doi.org/10.1124/jpet.107.121715
  4. J. Cummings, S. Isaacson, R. Mills, H. Williams, K. Chi-Burris, A. Corbett, R. Dhall and C. Ballard, Lancet, 383, 533 (2014); https://doi.org/10.1016/S0140-6736(13)62106-6
  5. S.M. Stahl, CNS Spectr., 21, 271 (2016); https://doi.org/10.1017/S1092852916000407
  6. R. Navaneeswari, M. Rajasekhar, K. Ramesh Babu, G. Buchappa and G. Vaidyanathan, Int. Res. J. Mod. Eng. Technol. Sci., 4, 4510 (2022).
  7. I. Radic, M. Runje and S. Babic, J. Pharm. Biomed. Anal., 201, 114091 (2021); https://doi.org/10.1016/j.jpba.2021.114091
  8. E. Ezzeldin, M. Iqbal, Y.A. Asiri, A.A. Ali and T. El-Nahhas, J. Chromatogr. B, 1143, 122015 (2020); https://doi.org/10.1016/j.jchromb.2020.122015
  9. S. Wang, Y. Wang, S. Gao, Y. Zhang, H. Wang, L. Zhao, K. Bi, S. Wang and X. Chen, J. Pharm. Anal., 7, 406 (2017); https://doi.org/10.1016/j.jpha.2017.07.004
  10. P. Nagaraju and V.L. Kantu, World J. Pharm. Life Sci., 8, 156 (2022).
  11. M.C. Damle, R.R. Pardeshi and S.R. Bidkar, Int. J. Pharm. Pharm. Sci., 15, 17 (2023); https://doi.org/10.22159/ijpps.2023v15i10.48820
  12. K.K. Aalapati, A. Singh and R.S. Patnaik, J. Chromatogr. Sci., 60, 357 (2022); https://doi.org/10.1093/chromsci/bmab069
  13. ICH Guideline: Stability Testing of New Drug Substances and Products, Q1A (R2), Current Step 4 version (2003).
  14. R.V. Bhupatiraju, S.R. Battula, M.V.N.R. Kapavarapu and V.R. Mandapati, Ann. Pharm. Fr., 81, 64 (2023); https://doi.org/10.1016/j.pharma.2022.06.012
  15. B.H.R. Varma and B.S. Rao, Res. J. Chem. Environ., 27, 54 (2023); https://doi.org/10.25303/2702rjce054061
  16. G.B. Koduri, H.B. Bollikolla, D. Ramachandran and N. Srinivasu, Pharm. Sci., 24, 291 (2018).
  17. ICH Guideline: Validation of Analytical Procedures: Text and Methodology Q2 (R1), Current Step 4 version (2005).
  18. P.M.K. Raju, P. Shyamala, B. Venkata Narayana, H.S.N.R. Dantuluri and R.V. Bhupatiraju, Ann. Pharm. Fr., 80, 837 (2022); https://doi.org/10.1016/j.pharma.2022.03.003
  19. R.V. Bhupatiraju and B.S. Rao, Res. J. Pharm. Technol., 15, 5158 (2022); https://doi.org/10.52711/0974-360X.2022.00868
  20. R.V. Bhupatiraju, S.K. Battula, P. Peddi and V.S. Tangeti, J. Chem. Metrol., 2, 181 (2023); https://doi.org/10.25135/jcm.98.2311.2975
  21. V.B. Rajesh, B.B. Kasimala, L. Nagamalla and F. Sayed, Anal. Sci. Technol., 37, 98 (2024); https://doi.org/10.5806/AST.2024.37.2.98
  22. R.V. Bhupatiraju, B.S. Kumar, V.S. Tangeti, K. Rekha and F. Sayed, Toxicol. Int., 31, 321 (2024); https://doi.org/10.18311/ti/2024/v31i2/36370
Read More
Author biographies is not available.
Statistic
Read Counter : 0 Download : 0