TiO2-embedded molecularly imprinted polymer as electrochemical sensor for ultrasensitive determination of glycopyrronium bromide

Original scientific paper

Authors

  • Zehra Dogan Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, Ankara, Türkiye; Ankara University, Graduate School of Health Sciences, Ankara, Türkiye https://orcid.org/0009-0005-8399-0891
  • Ensar Piskin Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, Ankara, Türkiye; Ankara University, Graduate School of Health Sciences, Ankara, Türkiye https://orcid.org/0009-0002-0521-6831
  • Ahmet Cetinkaya University of Health Sciences, Gülhane Faculty of Pharmacy, Department of Analytical Chemistry, Ankara, Türkiye https://orcid.org/0000-0001-5014-0907
  • Esen Bellur Atici Gebze Technical University, Department of Chemistry, Kocaeli, Türkiye; DEVA Holding A.S., R&D Center, Tekirdağ, Türkiye https://orcid.org/0000-0002-4093-441X
  • Sibel Aysil Ozkan Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, 06100, Tandogan, Ankara, Turkey https://orcid.org/0000-0001-7494-3077

DOI:

https://doi.org/10.5599/admet.3102

Keywords:

Electrochemical detection, photopolymerization method, glassy carbon electrode, drug analysis, nanomaterial, real sample

Abstract

Background and purpose: The precise quantification and quality evaluation of glycopyrronium bromide (GLB), a long-acting muscarinic antagonist widely used in the treatment of chronic obstructive pulmonary disease, requires the development of advanced analytical methodologies capable of achieving high sensitivity, accuracy, and selectivity to ensure therapeutic efficacy and formulation integrity. This study aims to overcome the limitations of conventional methods by developing a rapid, cost-effective method for determining GLB. Experimental approach: To achieve this, titanium dioxide nanoparticles (TiO2 NPs) were initially applied onto a glassy carbon electrode surface to provide an enhanced surface area and increased conductivity. Subsequently, a TiO2 nanoparticle-supported molecularly imprinted polymer (MIP) film was synthesized via photopoly­merization using GLB as the template molecule, 4-amminobenzoic acid (4-ABA) as the functional monomer, ethylene glycol dimethacrylate as the crosslinking agent, and 2-hydroxyethyl methacrylate (HEMA) as the basic monomer. Key results: The optimized GLB/4-ABA@TiO2 NPs/MIP- sensor demonstrated outstanding analytical performance, achieving ultra-low picomolar detection limits. The system exhibited superior selectivity (confirmed by high imprinting factor), excellent repeatability and reproducibility, and satisfactory stability. It was successfully applied to the accurate measurement of GLB in both commercial serum and pharmaceutical formulations. Conclusion: The designed nanomaterial-embedded MIP-based electro­chemical system presented here offers a highly successful, sensitive, and selective method for GLB determination. The work significantly advances knowledge in the field of analytical medicine and drug monitoring by providing a fast, robust alternative for routine clinical and quality-control tracking of GLB.

Downloads

Download data is not yet available.

References

[1] C.F. Vogelmeier, G.J. Criner, F.J. Martinez, A. Anzueto, P.J. Barnes, J. Bourbeau, B.R. Celli, R. Chen, M. Decramer, L.M. Fabbri, P. Frith, D.M.G. Halpin, M.V.L. Varela, M. Nishimura, N. Roche, R. Rodriguez-Roisin, D.D. Sin, D. Singh, R. Stockley, J. Vestbo, J.A. Wedzicha, A. Agustí. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. American journal of respiratory and critical care medicine 195 (2017) 557-582. https://doi.org/10.1164/rccm.201701-0218PP DOI: https://doi.org/10.1164/rccm.201701-0218PP

[2] E. Gordon, S.C. Lazarus, Management of chronic obstructive pulmonary disease: Moving beyond the asthma algorithm. Journal of Allergy and Clinical Immunology 124 (2009) 873-880. https://doi.org/10.1016/j.jaci.2009.09.040 DOI: https://doi.org/10.1016/j.jaci.2009.09.040

[3] L.A. Hussein, N. Magdy, H.Z. Yamani. Stable glycopyrronium bromide solid contact ion selective potentiometric sensors using multi-walled carbon nanotubes, polyaniline nanoparticles and polyaniline microparticles as ion-to-electron transducers: A comparative study. Sensors and Actuators B: Chemical 247 (2017) 436-444. https://doi.org/10.1016/j.snb.2017.03.021 DOI: https://doi.org/10.1016/j.snb.2017.03.021

[4] D. Singh, A. Ravi, F. Reid, H. Buck, G. O’Connor, G. Down. Bronchodilator effects, pharmacokinetics and safety of PSX1002-GB, a novel glycopyrronium bromide formulation, in COPD patients; a randomised crossover study. Pulmonary Pharmacology & Therapeutics 37 (2016) 9-14. https://doi.org/10.1016/j.pupt.2016.01.003 DOI: https://doi.org/10.1016/j.pupt.2016.01.003

[5] D. Nebiu, M. Walter, B. Lachmann, H. Kopelent, C.R. Noe. Determination of (R,R)-glycopyrronium bromide and its related impurities by ion-pair HPLC. Die Pharmazie - An International Journal of Pharmaceutical Sciences 62 (2007) 406-410. https://doi.org/10.1691/ph.2007.6.6220

[6] M.L. Storme, R.S. t’Kindt, W. Goeteyn, K. Reyntjens, J.F. Van Bocxlaer. Quantitative determination of glycopyrrolate in human plasma by liquid chromatography-electrospray ionization mass spectrometry: The use of a volatile ion-pairing agent during both liquid-liquid extraction and liquid chromatography. Journal of Chromatography B 876 (2008) 24-30. https://doi.org/10.1016/j.jchromb.2008.10.013 DOI: https://doi.org/10.1016/j.jchromb.2008.10.013

[7] G.R. Murray, T.N. Calvey, N.E. Williams, K. Chan. Quantitative capillary column gas chromatographic method for the determination of glycopyrronium in human plasma. Journal of chromatography. B, Biomedical sciences and applications 308 (1984) 143-151. https://doi.org/10.1016/0378-4347(84)80204-2 DOI: https://doi.org/10.1016/0378-4347(84)80204-2

[8] Y.M. Youssef, M.A. Mahrouse, E.A. Mostafa. Plackett-Burman and face-centered composite designs for development and optimization of chromatographic method for the simultaneous determination of glycopyrronium, indacaterol and mometasone in their fixed dose combination inhaler - Green profile assessment. Journal of Pharmaceutical and Biomedical Analysis 234 (2023) 115553. https://doi.org/10.1016/j.jpba.2023.115553 DOI: https://doi.org/10.1016/j.jpba.2023.115553

[9] M.Y. Ebeid, B.A. Moussa, A.A.A. Malak. Analysis of some antispasmodic drugs: oxyphencyclimine and glycopyrronium bromide. Pharmaceutisch Weekblad Scientific Edition 8 (1986) 252-258. https://doi.org/10.1007/BF01960069 DOI: https://doi.org/10.1007/BF01960069

[10] L. Uzun, A.P.F. Turner. Molecularly-imprinted polymer sensors: Realising their potential. Biosens Bioelectron 76 (2016) 131-144. https://doi.org/10.1016/j.bios.2015.07.013 DOI: https://doi.org/10.1016/j.bios.2015.07.013

[11] A. Cetinkaya, S. Bilge, L. Karadurmus, A. Sınağ, S.A. Ozkan. The role and the place of ionic liquids in molecularly imprinted polymer-based electrochemical sensors development for sensitive drug assay. TrAC - Trends in Analytical Chemistry 147 (2022) 116512. https://doi.org/10.1016/j.trac.2021.116512 DOI: https://doi.org/10.1016/j.trac.2021.116512

[12] X. Wang, L. Wang, X. He, Y. Zhang, L. Chen. A molecularly imprinted polymer-coated nanocomposite of magnetic nanoparticles for estrone recognition. Talanta 78 (2009) 327-332. https://doi.org/10.1016/j.talanta.2008.11.024 DOI: https://doi.org/10.1016/j.talanta.2008.11.024

[13] I. Sulym, A. Cetinkaya, M. Yence, M.E. Çorman, L. Uzun, S.A. Ozkan. Novel electrochemical sensor based on molecularly imprinted polymer combined with L-His-MWCNTs@PDMS-5 nanocomposite for selective and sensitive assay of tetracycline. Electrochimica Acta 430 (2022) 141102. https://doi.org/10.1016/j.electacta.2022.141102 DOI: https://doi.org/10.1016/j.electacta.2022.141102

[14] E. Piskin, F.A. Korkut, A. Cetinkaya, S.A. Ozkan. Highly selective and sensitive detection of atorvastatin from using a MIP-based electrochemical sensor. Journal of Pharmaceutical and Biomedical Analysis Open 5 (2025) 100061. https://doi.org/10.1016/j.jpbao.2025.100061 DOI: https://doi.org/10.1016/j.jpbao.2025.100061

[15] E. Piskin, A. Cetinkaya, M.A. Unal, E. Özgür, E.B. Atici, L. Uzun, S.A. Ozkan. A molecularly imprinted polymer-based detection platform confirmed through molecular modeling for the highly sensitive and selective analysis of ipratropium bromide. Journal of Pharmaceutical and Biomedical Analysis 248 (2024) 116283. https://doi.org/10.1016/j.jpba.2024.116283 DOI: https://doi.org/10.1016/j.jpba.2024.116283

[16] M. Emin Çorman, A. Cetinkaya, C. Armutcu, L. Uzun, S.A. Ozkan. Designing of ZnO nanoparticles oriented interface imprinted electrochemical sensor for fluoxetine detection. Bioelectrochemistry 152 (2023) 108411. https://doi.org/10.1016/j.bioelechem.2023.108411 DOI: https://doi.org/10.1016/j.bioelechem.2023.108411

[17] E. Piskin, A. Cetinkaya, M.A. Unal, B. Pérez-López, U.B. Gunatilake, S. Sene, Y. Guari, J. Larionova, E. Baldrich, S.A. Ozkan. Designing a molecularly imprinted polymer-based electrochemical sensor for the sensitive and selective detection of the antimalarial chloroquine phosphate. Microchimica Acta 191 (2024) 741. https://doi.org/10.1007/s00604-024-06820-4. DOI: https://doi.org/10.1007/s00604-024-06820-4

[18] N. Aristov, A. Habekost, Cyclic voltammetry - a versatile electrochemical method ınvestigating electron transfer processes. World Journal of Chemical Education 3 (2015) 115-119. https://pubs.sciepub.com/wjce/3/5/2/index.html

[19] A. Procedures, Guidance for Industry Q2B Validation of Analytical Procedures: Methodology, 20857 (1996) 301-827. http://www.fda.gov/cber/guidelines.htm

[20] S.A. Ozkan, J.M. Kauffmann, P. Zuman, Electroanalysis in Biomedical and Pharmaceutical Sciences, Springer Berlin Heidelberg, Berlin, Heidelberg, 2015. https://doi.org/10.1007/978-3-662-47138-8 DOI: https://doi.org/10.1007/978-3-662-47138-8

[21] M.J. Rumpler, R.A. Sams, P. Colahan. Validation of a liquid chromatography-tandem mass spectrometry method for quantification of glycopyrrolate in horse plasma. Journal of Analytical Toxicology 35 (2011) 656-664. https://doi.org/10.1093/anatox/35.9.656 DOI: https://doi.org/10.1093/anatox/35.9.656

[22] Y.A. Salem, M.E. Hammouda, N.M. Saleh, M.A.A. El-Enin, S.M. El-Ashry. Validated ion pair chromatographic method for simultaneous determination and in vitro dissolution studies of indacaterol and glycopyrronium from inhaled capsule dosage form. Spectrochimica Acta Part A 204 (2018) 464-474. https://doi.org/10.1016/j.saa.2018.06.078 DOI: https://doi.org/10.1016/j.saa.2018.06.078

[23] S. Zayed, F. Belal. Capillary electrophoresis with field-amplified sample stacking for simultaneous determination of indacaterol and glycopyrronium in inhaler capsules: Application to human plasma and urine. Microchemical Journal 155 (2020) 104779.https://doi.org/10.1016/j.microc.2020.104779 DOI: https://doi.org/10.1016/j.microc.2020.104779

Downloads

Published

08-12-2025

Issue

Vol. 13 No. 6 (2025)

Section

Pharmaceutical and biomedical analysis

License

Copyright (c) 2025 Zehra Dogan, Ensar Piskin, Ahmet Cetinkaya, Esen Bellur Atici, Sibel Aysil Ozkan

Creative Commons License

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

How to Cite

TiO2-embedded molecularly imprinted polymer as electrochemical sensor for ultrasensitive determination of glycopyrronium bromide: Original scientific paper. (2025). ADMET and DMPK, 13(6), Article 3102. https://doi.org/10.5599/admet.3102

Funding data