Home Metalloporphyrin-mediated oxidative degradation of risperidone under mild conditions: an LC-MS/MS study
Article
Licensed
Unlicensed Requires Authentication

Metalloporphyrin-mediated oxidative degradation of risperidone under mild conditions: an LC-MS/MS study

  • Midhuna Subash ORCID logo EMAIL logo , Rachel Bijoy , Mukund S. Chorghade and Bhaskar N. Thorat
Published/Copyright: February 18, 2025
Pure and Applied Chemistry
From the journal Pure and Applied Chemistry Volume 97 Issue 5

Abstract

This study examines the oxidative breakdown of an antipsychotic drug risperidone utilizing a metalloporphyrin catalyst in a controlled, constrained amount of time and moderate reaction conditions. Analyzing products and tracking the oxidative degradation process using LC-MS/MS analysis gave precise information on the reaction products and defined structural changes. The study investigated the fragmentation patterns of risperidone’s oxidative breakdown products, delving into the mechanisms underlying each fragmentation pathway. Our work highlights the creation of site-specific metabolites. Risperidone-N-oxide was identified as a significant oxidative product along with minimal quantities of in vivo metabolite, 9-hydroxyrisperidone.

Keywords: 9-hydroxyrisperidone; LC-MS/MS; metalloporphyrins; risperidone; risperidone-N-oxide; VCCA-2024
Corresponding author: Midhuna Subash, Department of Chemistry, Institute of Chemical Technology, ICT Mumbai-IOC Odisha Campus, Bhubaneswar, 751013, India, e-mail:
Article note: A collection of invited papers based on presentations at the Virtual Conference on Chemistry and its Applications held on 12–16 August 2024.

Acknowledgments

The authors are thankful to Clearsynth Labs, Hyderabad for providing all the API standards and the facility to carry out all the analytical research, including LC-MS/MS.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Midhuna Subash: design of the project, analysis, interpretation of data, writing-draft manuscript. Rachel Bijoy: suggestions for the work. Mukund S. Chorghade: design of the project, review and editing. Bhaskar N. Thorat: review and editing.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

References

1. Hill, D. R.; Celebuski, J. E.; Pariza, R. J.; Chorghade, M. S.; Levenberg, M.; Pagano, T.; Cleary, G.; West, P.; Whittern, D. Novel Macrolides via Meso-Tetraarylmetalloporphyrin Assisted Oxidations. Tetrahedron Lett. 1996, 37 (6), 787–790. https://doi.org/10.1016/0040-4039(95)02392-5.Search in Google Scholar

2. Simões, M. M. Q.; Neves, C. M. B.; Pires, S. M. G.; Neves, M. G. P. M. S.; Cavaleiro, J. A. S. Mimicking P450 Processes and the Use of Metalloporphyrins. Pure Appl. Chem. 2013, 85 (8), 1671–1681. https://doi.org/10.1351/PAC-CON-12-11-15.Search in Google Scholar

3. Barona-Castaño, J. C.; Carmona-Vargas, C. C.; Brocksom, T. J.; De Oliveira, K. T.; Graça, M.; Neves, P. M. S.; Amparo, M.; Faustino, F. Porphyrins as Catalysts in Scalable Organic Reactions. Molecules 2016, 21 (3), 310. https://doi.org/10.3390/molecules21030310.Search in Google Scholar PubMed PubMed Central

4. Neves, C. M. B.; Simões, M. M. Q.; Domingues, F. M. J.; Neves, M. G. P. M. S.; Cavaleiro, J. A. S. Biomimetic Oxidation of Carbamazepine with Hydrogen Peroxide Catalyzed by a Manganese Porphyrin. Quim. Nova 2012, 35 (7), 1477–1481. https://doi.org/10.1590/S0100-40422012000700033.Search in Google Scholar

5. Bernadou, J.; Bonnafous, M.; Loiseau, G. Labat P.; Biomimetic, B. M. Oxidation of Acetaminophen and Ellipticine Derivatives WithWater-Soluble Metalloporphyrins Associated to Potassium Monopersulfate. Pharmacology 1990, 19 (2), 360–365.10.1016/S0090-9556(25)07127-2Search in Google Scholar

6. Melo, A. J. B.; Iamamoto, Y.; Maestrin, A. P. J.; Smith, J. R. L.; Santos, M. D.; Lopes, N. P.; Bonato, P. S. Biomimetic Oxidation of Praziquantel Catalysed by Metalloporphyrins. J. Mol. Catal. A Chem. 2005, 226 (1), 23–31. https://doi.org/10.1016/j.molcata.2004.09.015.Search in Google Scholar

7. Sousa-Junior, J. N.; Rocha, B. A.; Assis, M. D.; Peti, A. P. F.; Moraes, L. A. B.; Iamamoto, Y.; Gates, P. J.; de Oliveira, A. R. M.; Lopes, N. P. Biomimetic Oxidation Studies of Monensin A Catalyzed by Metalloporphyrins: Identification of Hydroxyl Derivative Product by Electrospray Tandem Mass Spectrometry. Rev. Bras. Farmacogn. 2013, 23 (4), 621–629. https://doi.org/10.1590/S0102-695X2013005000053.Search in Google Scholar

8. Che, C.-M.; Huang, J.-S. Metalloporphyrin-Based Oxidation Systems: From Biomimetic Reactions to Application in Organic Synthesis. Chem. Commun. 2009, 27, 3996–4015. https://doi.org/10.1039/b901221d.Search in Google Scholar PubMed

9. Chorghade, M. S.; Dezaro, D. A.; Hill, D. R.; Lee, E. C.; Pariza, R. J.; Andersen, J. V.; Hansen, K. T.; Dolphin, D. H. Metalloporphyrins as Chemical Mimics of Cytochrome P-450 Systems. Bioorganic Med. Chem. Lett. 1994, 4 (24), 2867–2870. https://doi.org/10.1016/S0960-894X(01)80830-1.Search in Google Scholar

10. Balogh, G. T.; Keseru, G. M. Metalloporphyrin Mediated Biomimetic Oxidations. A Useful Tool for the Investigation of Cytochrome P450 Catalyzed Oxidative Metabolism. Arkivoc 2004, 2004 (7), 124–139. https://doi.org/10.3998/ark.5550190.0005.710.Search in Google Scholar

11. Gonsalves, A. M. d. A. R.; Varejão, J. M. T. B.; Pereira, M. M. Some New Aspects Related to the Synthesis of Meso‐substituted Porphyrins. J. Heterocycl. Chem. 1991, 28, 635–640. https://doi.org/10.1002/jhet.5570280317.Search in Google Scholar

12. Lindsey, J. S.; Wagner, R. W. Investigation of the Synthesis of Ortho-Substituted Tetraphenylporphyrins. J. Org. Chem. 1989, 54 (4), 828–836. https://doi.org/10.1021/jo00265a021.Search in Google Scholar

13. Schaab, E. H.; Crotti, A. E. M.; Iamamoto, Y.; Kato, M. J.; Lotufo, L. V. C.; Lopes, N. P. Biomimetic Oxidation of Piperine and Piplartine Catalyzed by Iron(III) and Manganese(III) Porphyrins. Biol. Pharm. Bull. 2010, 33 (5), 912–916. https://doi.org/10.1248/bpb.33.912.Search in Google Scholar PubMed

14. Bauermeister, A.; Aguiar, F. A.; Marques, L. M. M.; Malta, J. D. S.; Barros, F.; Callejon, D. R.; De Oliveira, A. R. M.; Lopes, N. P. In Vitro Metabolism Evaluation of the Ergot Alkaloid Dihydroergotamine: Application of Microsomal and Biomimetic Oxidative Model. Planta Med. 2016, 82 (15), 1368–1373. https://doi.org/10.1055/s-0042-111732.Search in Google Scholar PubMed

15. Olesen, O. V.; Linnet, K. Simplified High-Performance Liquid Chromatographic Method for Determination of Risperidone and 9-Hydroxyrisperidone in Serum from Patients Comedicated with Other Psychotropic Drugs. J. Chromatogr. B Biomed. Appl. 1997, 698 (1–2), 209–216. https://doi.org/10.1016/S0378-4347(97)00302-2.Search in Google Scholar PubMed

16. Möller, H.-J. Risperidone: A Review. Expert Opin. Pharmacother. 2005, 6 (5), 803–818. https://doi.org/10.1517/14656566.6.5.803.Search in Google Scholar PubMed

17. Grant, S.; Fitton, A. Risperidone. Drugs 1994, 48 (2), 253–273. https://doi.org/10.2165/00003495-199448020-00009.Search in Google Scholar PubMed

18. Noto, C.; Ota, V. K.; Gadelha, A.; Noto, M. N.; Barbosa, D. S.; Bonifácio, K. L.; Nunes, S. O.; Cordeiro, Q.; Belangero, S. I.; Bressan, R. A.; Maes, M.; Brietzke, E. Oxidative Stress in Drug Naïve First Episode Psychosis and Antioxidant Effects of Risperidone. J. Psychiatr. Res. 2015, 68, 210–216. https://doi.org/10.1016/j.jpsychires.2015.07.003.Search in Google Scholar PubMed

19. Suthar, A. P.; Dubey, S. A.; Patel, S. R.; Shah, A. M. Determination of Risperidone and Forced Degradation Behavior by HPLC in Tablet Dosage Form. Int. J. PharmTech Res. 2009, 1 (3), 568–574.Search in Google Scholar

20. Dedania, Z. R.; Dedania, R. R.; Sheth, N. R.; Patel, J. B.; Patel, B. Stability Indicating HPLC Determination of Risperidone in Bulk Drug and Pharmaceutical Formulations. Int. J. Anal. Chem. 2011, 2011, 1–6. https://doi.org/10.1155/2011/124917.Search in Google Scholar PubMed PubMed Central

21. Sattanathan, P.; Babu, J. M.; Vyas, K.; Reddy, R. B.; Rajan, S. T.; Sudhakar, P. Structural Studies of Impurities of Risperidone by Hyphenated Techniques. J. Pharm. Biomed. Anal. 2006, 40 (3), 598–604. https://doi.org/10.1016/j.jpba.2005.10.034.Search in Google Scholar PubMed

22. Magar, L. P.; Zaware, B. H.; Laheru, C. J.; Singh, D.; Takate, S. J.; Gupta, M. K. Determination of Impurities of Risperidone API by Ultra Performance Liquid Chromatography (UPLC). Rasayan J. Chem. 2020, 12 (02), 940–948. https://doi.org/10.31788/RJC.2020.1325632.Search in Google Scholar

23. Chorghade, M. S.; Dolphin, D.; Dupré, D.; Hill, D. R.; Lee, E. C.; Wijesekera, T. P. Improved Protocols for the Synthesis and Halogenation of Sterically Hindered Metalloporphyrins. Synthesis (Stuttg) 1996, 1996 (11), 1320–1324. https://doi.org/10.1055/s-1996-4401.Search in Google Scholar

24. Adler, A. D.; Longo, F. R.; Kampas, F.; Kim, J. On the Preparation of Metalloporphyrins. J. Inorg. Nucl. Chem. 1970, 32 (7), 2443–2445. https://doi.org/10.1016/0022-1902(70)80535-8.Search in Google Scholar

25. Fodor, M. A.; Szabó, P.; Lendvay, G.; Horváth, O. Characterization of the UV-Visible Absorption Spectra of Manganese(III) Porphyrins with Time-Dependent Density Functional Theory Calculations. Zeitschrift für Phys. Chemie 2022, 236 (1), 27–51. https://doi.org/10.1515/zpch-2020-1787.Search in Google Scholar

26. Skibiński, R.; Komsta, Ł.; Inglot, T. Characterization of Paliperidone Photodegradation Products by LC-Q-TOF Multistage Mass Spectrometry. Biomed. Chromatogr. 2016, 30 (6), 894–901. https://doi.org/10.1002/bmc.3625.Search in Google Scholar PubMed

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/pac-2024-0352).

Published Online: 2025-02-18
Published in Print: 2025-05-26

© 2025 IUPAC & De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. In this issue
  3. Research Articles
  4. Efficient degradation of 1,2-dichlorobenzene using heterogeneous catalytic ozonation over metal loaded gamma alumina catalysts
  5. Effect of chemical modification using glyoxylic acid on the stability of α-amylase from Aspergillus fumigatus
  6. A new, innovative, simple method to determine the concentration of phosphate and sulphate ions in an aqueous extract of plants using conductometric titration
  7. Metalloporphyrin-mediated oxidative degradation of risperidone under mild conditions: an LC-MS/MS study
  8. Synthesis of novel ternary herbicide-layered double hydroxide hybrids via the ion exchange method
  9. Water Quality Index and the quality of freshwater resource uMhlathuze river, Kwazulu-Natal, South Africa: A Review
  10. Experimental ‘in-Vitro’ investigation on bio-chemical constituents, radical scavenging activity, and reducing power assay of cow urine
  11. Enhanced biofilm disruption in ESKAPE pathogens through synergistic activity of EPS degrading enzymes
  12. Green synthesis of silver nanoparticles using a bioflocculant produced by a kombucha tea yeast isolate for antimicrobial and biosafety testing
  13. Characterization of metabolite compounds from endophytic fungi associated with white turi plant (Sesbania grandiflora) and their antibacterial activity
  14. Enhanced photocatalytic degradation of methylene blue dye using TiO2 nanoparticles obtained via chemical and green synthesis: a comparative analysis
  15. Characterization of electrocatalysts for the oxygen evolution reaction OER: a bi-metal study IrM oxides (Ru, and Au)
  16. Development of a second harmonic generation microscope optimized for biomaterial studies
https://doi.org/10.1515/pac-2024-0352
Keywords for this article
9-hydroxyrisperidone; LC-MS/MS; metalloporphyrins; risperidone; risperidone-N-oxide; VCCA-2024

Articles in the same Issue

  1. Frontmatter
  2. In this issue
  3. Research Articles
  4. Efficient degradation of 1,2-dichlorobenzene using heterogeneous catalytic ozonation over metal loaded gamma alumina catalysts
  5. Effect of chemical modification using glyoxylic acid on the stability of α-amylase from Aspergillus fumigatus
  6. A new, innovative, simple method to determine the concentration of phosphate and sulphate ions in an aqueous extract of plants using conductometric titration
  7. Metalloporphyrin-mediated oxidative degradation of risperidone under mild conditions: an LC-MS/MS study
  8. Synthesis of novel ternary herbicide-layered double hydroxide hybrids via the ion exchange method
  9. Water Quality Index and the quality of freshwater resource uMhlathuze river, Kwazulu-Natal, South Africa: A Review
  10. Experimental ‘in-Vitro’ investigation on bio-chemical constituents, radical scavenging activity, and reducing power assay of cow urine
  11. Enhanced biofilm disruption in ESKAPE pathogens through synergistic activity of EPS degrading enzymes
  12. Green synthesis of silver nanoparticles using a bioflocculant produced by a kombucha tea yeast isolate for antimicrobial and biosafety testing
  13. Characterization of metabolite compounds from endophytic fungi associated with white turi plant (Sesbania grandiflora) and their antibacterial activity
  14. Enhanced photocatalytic degradation of methylene blue dye using TiO2 nanoparticles obtained via chemical and green synthesis: a comparative analysis
  15. Characterization of electrocatalysts for the oxygen evolution reaction OER: a bi-metal study IrM oxides (Ru, and Au)
  16. Development of a second harmonic generation microscope optimized for biomaterial studies
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 2.10.2025 from https://www.degruyterbrill.com/document/doi/10.1515/pac-2024-0352/html?srsltid=AfmBOorbKQGZ0c0cMpIQfQCnCYnXfj5ggP_ebglxJo5gFER6JwrGUNRx
Scroll to top button