SpringerLink
Log in

Flow injection tyrosinase biosensor for direct determination of acetaminophen in human urine

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

An amperometric biosensor compatible with a flow injection analysis (FIA) for highly selective determination of acetaminophen (APAP) in a sample of human urine was developed. This biosensor is also suitable for use in the routine pharmaceutical practice. To prove this statement, two different commercially available pharmaceutical formulations were analyzed. This nano-(bio)electroanalytical device was made from a commercially available screen-printed carbon electrode covered by a thin layer of non-functionalized graphene (NFG) as amperometric transducer. A biorecognition layer was prepared from mushroom (Agaricus bisporus) tyrosinase (EC 1.14.18.1) cross-linked using glutaraldehyde, where resulting aggregates were covered by Nafion®, a known ion exchange membrane. Owing to the use of tyrosinase and presence of NFG, the developed analytical instrument is able to measure even at potentials of 0 V. Linear ranges differ according to choice of detection potential, namely up to 130 μmol L−1 at 0 V, up to 90 μmol L−1 at −0.1 V, and up to 70 μmol L−1 at −0.15 V. The first mentioned linear range is described by the equation Ip [μA] = 0.236 − 0.1984c [μmol L−1] and correlation coefficient r = 0.9987; this equation was used to quantify the content of APAP in each sample. The limit of detection of APAP was estimated to be 1.1 μmol L−1. A recovery of 96.8% (c = 25 μmol L−1, n = 5 measurements) was calculated. The obtained results show that FIA is a very selective method for APAP determination, being comparable to the chosen reference method of reversed-phase high-performance liquid chromatography.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Thailand)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ivey KJ, Settree P. Effect of paracetamol (acetaminophen) on gastric ionic fluxes and potential difference in man. Gut. 1976;17(11):916–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Clissold SP. Paracetamol and phenacetin. Drugs. 1986;32(4):46–59.

    Article  PubMed  Google Scholar 

  3. Hodis J. New facts about paracetamol, risks of overdose, intoxication and their management. Practical Pharm. 2015;11(3):90–2.

    Google Scholar 

  4. Lancaster EM, Hiatt JR, Zarrinpar A. Acetaminophen hepatotoxicity: an updated review. Arch Toxicol. 2015;89:193–9.

    Article  CAS  PubMed  Google Scholar 

  5. Myers RP, Li B, Fong A, Shaheen AA, Quan H. Hospitalizations for acetaminophen overdose: a Canadian population-based study from 1995 to 2004. BMC Public Health. 2007;7:143.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Björnsson ES. Drug-induced liver injury: an overview over the most critical compounds. Arch Toxicol. 2015;89:327–34.

    Article  CAS  PubMed  Google Scholar 

  7. Luque de Castro MD, Valcárcel M. Flow injection analysis of pharmaceuticals. J Pharm Biomed Anal. 1989;7(12):1291–300.

    Article  CAS  PubMed  Google Scholar 

  8. Mičová K, Friedecký D, Faber E, Polýnková A, Adam T. Flow injection analysis vs ultra high performance liquid chromatography coupled with tandem mass spectrometry for determination of imatinib in human plasma. Clin Chim Acta. 2010;411(23-24):1957–62.

    Article  CAS  PubMed  Google Scholar 

  9. Luque de Castro MD, Cases MV. Simultaneous determinations in flow injection analysis. A review. Analyst. 1984;109(4):413–9.

    Article  CAS  Google Scholar 

  10. Li Y, Chen SM. The electrochemical properties of acetaminophen on bare glassy carbon electrode. Int J Electrochem Sci. 2012;7:2175–87.

    CAS  Google Scholar 

  11. Vaughan PA, Scott LDL, McAller JF. Anal Chim Acta. 1991;248(2):361–5.

    Article  CAS  Google Scholar 

  12. Gilmartin MAT, Hart JP. Rapid detection of paracetamol using a disposable, surface-modified screen-printed carbon electrode. Analyst. 1994;119(11):2431–7.

    Article  CAS  Google Scholar 

  13. Fatibello-Filho O, Lupetti KO, Vieira IC. Chronoamperometric determination of paracetamol using an avocado tissue (Persea americana) biosensor. Talanta. 2001;55(4):685–92.

    Article  CAS  PubMed  Google Scholar 

  14. Garcia LF, Benjamin SR, Antunes RS, Lopes FM, Somerset VS, Gil ES. Solanum melongena polyphenol oxidase biosensor for the electrochemical analysis of paracetamol. Prep Biochem Biotechnol. 2016;46(8):850–5.

    Article  CAS  PubMed  Google Scholar 

  15. González-Sánchez MI, Rubio-Retama J, López-Cabarcos E, Valero E. Development of an acetaminophen amperometric biosensor based on peroxidase entrapped in polyacrylamide microgels. Biosens Bioelectron. 2011;26(5):1883–9.

    Article  CAS  PubMed  Google Scholar 

  16. Maghear A, Cristea C, Marian A, Marian IO, Sandulescu R. A novel biosensor for acetaminophen detection with Romanian clays and conductive polymeric films. Farmacia. 2013;61:1.

    CAS  Google Scholar 

  17. Tertis M, Florea A, Sandulescu R, Cristea C. Carbon based electrodes modified with horseradish peroxidase immobilized in conducting polymers for acetaminophen analysis. Sensors. 2013;13:4841–54.

    Article  CAS  PubMed  Google Scholar 

  18. Valero E, Varón R, García-Carmona F. Catalytic oxidation of acetaminophen by tyrosinase in the presence of l-proline: a kinetic study. Arch Biochem Biophys. 2003;416(2):218–26.

    Article  CAS  PubMed  Google Scholar 

  19. Rolff M, Schottenheim J, Decker H, Tuczek F. Copper–O2 reactivity of tyrosinase models towards external monophenolic substrates: molecular mechanism and comparison with the enzyme. Chem Soc Rev. 2011;40(7):4077–98.

    Article  CAS  PubMed  Google Scholar 

  20. Valero E, Varón R, García-Carmona F. Tyrosinase-mediated oxidation of acetaminophen to 4-acetamido-o-benzoquinone. Biol Chem. 2002;383(12):1931–9.

    Article  CAS  PubMed  Google Scholar 

  21. Calas-Blanchard C, Istamboulié G, Bontoux M, Plantard G, Goetz V, Noguer T. Biosensor-based real-time monitoring of paracetamol photocatalytic degradation. Chemosphere. 2015;131:124–9.

    Article  CAS  PubMed  Google Scholar 

  22. Mukaddam M, Litwiller E, Pinnau I. Gas sorption, diffusion, and permeation in Nafion. Macromolecules. 2016;49(1):280–6.

    Article  CAS  Google Scholar 

  23. Rocchitta G, Spanu A, Babudieri S, Latte G, Madeddu G, Galleri G, et al. Enzyme biosensors for biomedical applications: strategies for safeguarding analytical performances in biological fluids. Sensors. 2016;16(6):780.

    Article  CAS  Google Scholar 

  24. Albareda-Sirvent M, Merkoçi A, Alegret S. Configurations used in the design of screen-printed enzymatic biosensors. A review. Sensors Actuators B Chem. 2000;69(1-2):153–63.

    Article  CAS  Google Scholar 

  25. Shao Y, Wang J, Wu H, Liu J, Aksay IA, Lin Y. Graphene based electrochemical sensors and biosensors: a review. Electroanalysis. 2010;22(10):1027–36.

    Article  CAS  Google Scholar 

  26. Lin Y, Yantasee W, Wang J. Carbon nanotubes (CNTs) for the development of electrochemical biosensors. Front Biosci. 2005;10:492–505.

    Article  CAS  PubMed  Google Scholar 

  27. Baranowska I, Wilczek A. Simultaneous RP-HPLC determination of sotalol, metoprolol, alpha-hydroxymetoprolol, paracetamol and its glucuronide and sulfate metabolites in human urine. Anal Sci. 2009;25(6):769–72.

    Article  CAS  PubMed  Google Scholar 

  28. Abu-Qare AW, Abou-Donia MB. A validated HPLC method for the determination of pyridostigmine bromide, acetaminophen, acetylsalicylic acid and caffeine in rat plasma and urine. J Pharm Biomed Anal. 2001;26(5-6):939–47.

    Article  CAS  PubMed  Google Scholar 

  29. Vandeput M, Patris S, Silva H, Parsajoo C, Dejaeghere B, Martinez JA, et al. Application of a tyrosinase microreactor – detector in a flow injection configuration for the determination of affinity and dynamics of inhibitor binding. Sensors Actuators B Chem. 2017;248:385–94.

    Article  CAS  Google Scholar 

  30. He Y, Cussler EL. Ammonia permeabilities of perfluorosulfonic membranes in various ionic forms. J Membr Sci. 1992;68:43–52.

    Article  CAS  Google Scholar 

  31. Birch ME, Ruda-Eberenz TA, Chai M, Andrews R, Hatfield RL. Properties that influence the specific surface areas of carbon nanotubes and nanofibers. Ann Occup Hyg. 2013;57(9):1148–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Brownson DA, Foster CW, Banks CE. The electrochemical performance of graphene modified electrodes: an analytical perspective. Analyst. 2012;137(8):1815–23.

    Article  CAS  PubMed  Google Scholar 

  33. Sýs M, Žabčíková S, Červenka L, Vytřas K. Comparison of adsorptive with extractive strip** voltammetry in electrochemical determination of retinol. Potr S J F Sci. 2017;11(1):96–105.

    Article  Google Scholar 

  34. Zhu Y, Murali S, Cai W, Li X, Suk JW, Potts JR, et al. Graphene and graphene oxide: synthesis, properties, and applications. Adv Mater. 2010;22:3906–24.

    Article  CAS  PubMed  Google Scholar 

  35. Sheldon RA. Characteristic features and biotechnological applications of cross-linked enzyme aggregates (CLEAs). Appl Microbiol Biotechnol. 2011;92:467–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gil ES, Cout RO. Flavonoid electrochemistry: a review on the electroanalytical applications. Rev Bras. 2013;23:542–58.

    CAS  Google Scholar 

  37. Duckworth HW, Coleman JE. Physicochemical and kinetic properties of mushroom tyrosinase. J Biol Chem. 1970;245:1613–25.

    CAS  PubMed  Google Scholar 

  38. Solná R, Skládal P. Amperometric flow injection determination of phenolic compounds using a biosensor with immobilized laccase, peroxidase and tyrosinase. Electroanalysis. 2005;23:2137–46.

    Article  CAS  Google Scholar 

  39. Sýs M, Pekec B, Kalcher K, Vytřas K. Amperometric enzyme carbon paste-based biosensor for quantification of hydroquinone and polyphenolic antioxidant capacity. Int J Electrochem Sci. 2013;8:9030–40.

    Google Scholar 

  40. Gorton L. Carbon paste electrodes modified with enzymes, tissues, and cells. Electroanalysis. 1995;7(1):23–45.

    Article  CAS  Google Scholar 

  41. Calvo EJ, Danilowicz C. Amperometric enzyme electrodes. J Braz Chem Soc. 1997;8(1):563–74.

    CAS  Google Scholar 

  42. Santos AM, Vicentini FC, Deroco PB, Rocha-Filho RC, Fatibello-Filho O. Square-wave voltammetric determination of paracetamol and codeine in pharmaceutical and human body fluid samples using a cathodically pretreated boron-doped diamond electrode. J Braz Chem Soc. 2015;26(10):2159–68.

    CAS  Google Scholar 

  43. Lourenção BC, Medeiros RA, Rocha-Filho RC, Mazo LH, Fatibello-Filho O. Simultaneous voltammetric determination of paracetamol and caffeine in pharmaceutical formulations using a boron-doped diamond electrode. Talanta. 2009;78(3):748–52.

    Article  CAS  PubMed  Google Scholar 

  44. Babaei A, Khalilzadeh B, Afrasiabi M. A new sensor for the simultaneous determination of paracetamol and mefenamic acid in a pharmaceutical preparation and biological samples using copper(II) doped zeolite modified carbon paste electrode. J Appl Electrochem. 2010;40(8):1537–43.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Financial support from Faculty of Chemical Technology, University of Pardubice (project No. SGS-2019-003) and CEEPUS CIII-CZ-0212-10-1617 network for mobility funding are gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Prishtina, Str. Mother Teresa, 10 000, Prishtina, Republic of Kosovo

    Arbër Frangu & Tahir Arbneshi

  2. Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10, Pardubice, Czech Republic

    Arbër Frangu, Kateřina Pravcová, Petra Šilarová & Milan Sýs

Authors
  1. Arbër Frangu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kateřina Pravcová
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Petra Šilarová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tahir Arbneshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Milan Sýs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Milan Sýs.

Ethics declarations

Informed consent

The study was not aiming to investigate functions/diseases of the human body or a process of medical treatment; therefore, the administration of acetaminophen by the participant was not performed and the drug was used only for artificial spiking of commercial and the participant’s own urine sample. A healthy volunteer received a complete description of the study and gave written informed consent before providing the urine samples. The obtained sample of human urine was anonymized before the study. The ethical principles for medical research of the components of human beings have not been violated because no compounds other than acetaminophen (artificially enriched urine) were determined. Therefore, all experiments with human urine samples were done in accordance with the WMA Declaration of Helsinki, June 1964.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 668 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Frangu, A., Pravcová, K., Šilarová, P. et al. Flow injection tyrosinase biosensor for direct determination of acetaminophen in human urine. Anal Bioanal Chem 411, 2415–2424 (2019). https://doi.org/10.1007/s00216-019-01687-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-019-01687-4

Keywords

Search

Navigation