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A facile and eco-friendly fluorometric method for the determination of methotrexate and folic acid in biological samples based on hollow luminescent carbon dots and chemometrics method

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Abstract

A rapid, simple, and inexpensive spectrofluorimetric sensor has been developed for the simultaneous determination of methotrexate (MTX) and folic acid (FA) based on their interactions with hollow carbon dots (HCDs). Since the use of folic acid to cope with the toxic side effects of MTX in patients is essential, the simultaneous determination of these two compounds has been interesting. The results showed that  MTX could quench the fluorescence of HCDs with a dynamic quenching mechanism. The sensor exhibited a linear concentration range of 1.0 × 10–6–1.9 × 10–4 mol L−1 for MTX and 1.5 × 10–5–9.4 × 10–4 mol L−1 for FA and the obtained detection limits for MTX and FA were 1.6 × 10–7 and 5.0 × 10–7 mol L−1, respectively. The applicability of the method was investigated in the analysis of the urine samples and the partial least squares (PLS) method was used for the simultaneous determination of MTX and FA.

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References

  1. X. Xu, R. Ray, Gu. Yunlong, H.J. Ploehn, L. Gearheart, K. Raker, W.A. Scrivens, Electrophoretic analysis and purification of fluorescent single-walled carbon nanotube fragments. J. Am. Chem. Soc. 126, 12736–12737 (2004). https://doi.org/10.1021/ja040082h

    Article  CAS  PubMed  Google Scholar 

  2. S. Zhu, Q. Meng, L. Wang, J. Zhang, Y. Song, H. Jin, K. Zhang, H. Sun, H. Wang, B. Yang, Highly photoluminescent carbon dots for multicolor patterning, sensors, and bioimaging. Angew. Chem. Int. Ed. 125, 4045–4049 (2013). https://doi.org/10.1002/anie.201300519

    Article  CAS  Google Scholar 

  3. L. Li, H. Song, X. Chen, Hollow carbon microspheres prepared from polystyrene microbeads. Carbon 3, 596–599 (2006). https://doi.org/10.1016/j.carbon.2005.09.035

    Article  CAS  Google Scholar 

  4. L. Qiao, L. Ren, R. Zhang, J. Chen, X. Minggui, J. Liu, X. HaiJun, W. Liu, Z. Chang, X. Sun, Hollow carbon spheres embedded with VN quantum dots as an efficient cathode host for lithium-sulfur batteries. Energy Fuels 35, 10219–10226 (2021). https://doi.org/10.1021/acs.energyfuels.1c00716

    Article  CAS  Google Scholar 

  5. A.S. Rasal, S. Yadav, A. Yadav, A.A. Kashale, S.T. Manjunatha, A. Altaee, J.Y. Chang, Carbon quantum dots for energy applications: a review. ACS Appl. Nano Mater. 4, 6515–6541 (2021). https://doi.org/10.1021/acsanm.1c01372

    Article  CAS  Google Scholar 

  6. Z. Zhang, F. Xiao, J. Xi, T. Sun, S. Xiao, H. Wang, S. Wang, Y. Liu, Encapsulating Pd nanoparticles in double-shelled graphene@ carbon hollow spheres for excellent chemical catalytic property. Sci. Rep. 4, 1–5 (2014). https://doi.org/10.1038/srep04053

    Article  CAS  Google Scholar 

  7. C. Wu, X. Zhu, L. Ye, C. OuYang, H. Shuangquan, L. Lei, Y. Xie, Necklace-like hollow carbon nanospheres from the pentagon-including reactants: synthesis and electrochemical properties. Inorg. Chem. 45, 8543–8550 (2006). https://doi.org/10.1021/ic060827f

    Article  CAS  PubMed  Google Scholar 

  8. G. Hu, D. Ma, M. Cheng, L. Liu, X. Bao, Direct synthesis of uniform hollow carbon spheres by a self-assembly template approach. Chem. Comm. 17, 1948–1949 (2002). https://doi.org/10.1039/B205723A

    Article  Google Scholar 

  9. H. Ham, N.H. Park, S.S. Kim, H.W. Kim, Evidence of Ostwald ripening during evolution of micro-scale solid carbon spheres. Sci. Rep. 4, 1–4 (2014). https://doi.org/10.1038/srep03579

    Article  Google Scholar 

  10. O. Mkhari, T.D. Ntuli, N.J. Coville, E.N. Nxumalo, M.S. Maubane-Nkadimeng, A comparison of fluorescent N-doped carbon dots supported on the surface of hollow and solid carbon spheres, and solid silica spheres Diam. Relat. Mater. 118, 108500 (2021). https://doi.org/10.1016/j.diamond.2021.108500

    Article  CAS  Google Scholar 

  11. Y. Xiong, Y. Xie, Z. Li, W. Changzheng, R. Zhang, A novel approach to carbon hollow spheres and vessels from CCl4 at low temperatures. Chem. Comm. 7, 904–905 (2003). https://doi.org/10.1039/B211996J

    Article  Google Scholar 

  12. D.E. Thurston, I. Pysz, Chemistry and pharmacology of anticancer drugs (CRC Press. Taylor and Francis Group, Boca Raton, 2007)

    Google Scholar 

  13. W.A. Bleyer, The clinical pharmacology of methotrexate. new applications of an old drug. Cancer 41, 36–51 (1987). https://doi.org/10.1002/1097-0142(197801)41

    Article  Google Scholar 

  14. K. Hansson, H. Orrling, A. Blomgren, A. Isaksson, G. Schliamser, J. Heldrup, C.J. Pronk, Simultaneous determination of folate and methotrexate metabolites in serum by LC-MS/MS during high-dose methotrexate therapy. J. Chromatogr. 1186, 123007 (2021). https://doi.org/10.1016/j.jchromb.2021.123007

    Article  CAS  Google Scholar 

  15. A. Muñoz De La Peña, I. Durán Merás, A. Jiménez Girón, Four-way calibration applied to the simultaneous determination of folic acid and methotrexate in urine samples. Anal. Bioanal. Chem. 385, 1289–1297 (2006). https://doi.org/10.1007/s00216-006-0408-3

    Article  CAS  PubMed  Google Scholar 

  16. Z. Zhu, W. Hongwei, W. Shuchao, Z. Huang, Y. Zhu, L. Xi, Determination of methotrexate and folic acid by ion chromatography with electrochemical detection on a functionalized multi-wall carbon nanotube modified electrode. J. Chromatogr. A 1283, 62–67 (2013). https://doi.org/10.1016/j.chroma.2013.01.085

    Article  CAS  PubMed  Google Scholar 

  17. A.A. Ensafi, P. Nasr-Esfahani, B. Rezaei, Simultaneous detection of folic acid and methotrexate by an optical sensor based on molecularly imprinted polymers on dual-color CdTe quantum dots. Anal. Chim. Acta 996, 64–73 (2017). https://doi.org/10.1016/j.aca.2017.10.011

    Article  CAS  PubMed  Google Scholar 

  18. S. Tajik, H. Beitollahi, S. Shahsavari, F.Garkani Nejad, Simultaneous and selective electrochemical sensing of methotrexate and folic acid in biological fluids and pharmaceutical samples using Fe3O4/ppy/Pd nanocomposite modified screen printed graphite electrode. Chemosphere 291, 132736 (2022). https://doi.org/10.1016/j.chemosphere.2021.132736

    Article  CAS  PubMed  Google Scholar 

  19. S. Wold, M. Sjöström, L. Eriksson, PLS-regression: a basic tool of chemometrics. Chemom. Intell. Lab. Syst. 58, 109–130 (2001). https://doi.org/10.1016/S0169-7439(01)00155-1

    Article  CAS  Google Scholar 

  20. Q. Wang, X. Huang, Y. Long, X. Wang, H. Zhang, R. Zhu, L. Liang, P. Teng, H. Zheng, Hollow luminescent carbon dots for drug delivery. Carbon 59, 192–199 (2013). https://doi.org/10.1016/j.carbon.2013.03.009

    Article  CAS  Google Scholar 

  21. K.S. Novoselov, A.K. Geim, S.V. Morozov, D.-E. Jiang, Y. Zhang, S.V. Dubonos, I.V. Grigorieva, A.A. Firsov, Electric field effect in atomically thin carbon films. Science 306, 666–669 (2004). https://doi.org/10.1126/science.1102896

    Article  CAS  PubMed  Google Scholar 

  22. V. Booker, C. Halsall, N. Llewellyn, A. Johnson, R. Williams, Prioritising anticancer drugs for environmental monitoring and risk assessment purposes. Sci. Total Environ. 473, 159–170 (2014). https://doi.org/10.1016/j.scitotenv.2013.11.145

    Article  CAS  PubMed  Google Scholar 

  23. C. Sköld, S. Winiwarter, J. Wernevik, F. Bergström, L. Engström, R. Allen, K. Box, J. Comer, J. Mole, A. Hallberg, H. Lennernäs, Presentation of a structurally diverse and commercially available drug data set for correlation and benchmarking studies. J. Med. Chem. 49(23), 6660–6671 (2006). https://doi.org/10.1021/jm0506219

    Article  CAS  PubMed  Google Scholar 

  24. J. Chen, Y. Gao, X. ZhiBing, W. GenHua, Y. Chen, C. Zhu, A novel fluorescent array for mercury (II) ion in aqueous solution with functionalized cadmium selenide nanoclusters. Anal. Chim. Acta 577, 77–84 (2006). https://doi.org/10.1016/j.aca.2006.06.039

    Article  CAS  PubMed  Google Scholar 

  25. J. Flores, G.C. Rodríguez, A.E. Peñalvo et al., Capillary electrophoretic determination of methotrexate, leucovorin and folic acid in human urine. J. Chromatogr. B 819(1), 141–147 (2005). https://doi.org/10.1016/j.jchromb.2005.01.039

    Article  CAS  Google Scholar 

  26. K.K. Saindane, H. Talapadatur, U. Parab, V. Kumar, Simultaneous estimation of folic acid and methotrexate in tablet dosage form by high-performance liquid chromatography. World J. Pharm. Res. 11, 1662–1677 (2022). https://doi.org/10.20959/wjpr20224-23643

    Article  CAS  Google Scholar 

  27. F.G. Nejad, H. Beitollahi, I. Sheikhshoaie, Electrochemical sensing of methotrexate in the presence of folic acid using PAMAM dendrimer-functionalized multi-walled carbon nanotubes modified electrode. Anal. Methods (2023). https://doi.org/10.1039/D2AY02093A

    Article  PubMed  Google Scholar 

  28. S. Chutipongtanate, V. Thongboonkerd (2010) Systematic comparisons of artificial urine formulas for in vitro cellular study. Anal. Biochem. 402, 110–112 (2010). https://doi.org/10.1016/j.ab.2010.03.031

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors express their gratitude to Shiraz University Research Council for the financial support of this work.

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Correspondence to Javad Tashkhourian or Mojtaba Shamsipur.

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Alimohammadi, M., Tashkhourian, J., Mostafapour, S. et al. A facile and eco-friendly fluorometric method for the determination of methotrexate and folic acid in biological samples based on hollow luminescent carbon dots and chemometrics method. ANAL. SCI. 39, 1455–1464 (2023). https://doi.org/10.1007/s44211-023-00360-2

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