Microchimica Acta

, Volume 183, Issue 10, pp 2771–2778 | Cite as

Voltammetric determination of paracetamol using a glassy carbon electrode modified with Prussian Blue and a molecularly imprinted polymer, and ratiometric read-out of two signals

  • Yunlong Dai
  • Xueyan Li
  • Xiaojing Lu
  • Xianwen KanEmail author
Original Paper


The authors report on a ratiometric electrochemical sensor for paracetamol (PR) which was fabricated by successively electropolymerizing a layer of Prussian blue (PB) and a layer of molecularly imprinted polypyrrole (MIP) on the surface of a glassy carbon electrode (GCE). The binding of PR molecules to the MIP has two effects: The first is an increase of the oxidation current for PR at 0.42 V (vs. SCE), and the second is a decrease in the current for PB (at 0.18 V) due to partial blocking of the channels which results in reduced electron transmissivity. Both currents, and in particular their ratio, can serve as analytical information. Under optimized conditions, the sensor displays enhanced sensitivity for PR in the 1.0 nM to 0.1 mM concentration range and a 0.53 nM lower limit of detection. The sensor was applied to the determination of PR in tablets and urines where it gave recoveries in the range between 94.6 and 104.9 %. This dual-signal (ratiometric) detection scheme (using electropolymerized Prussian Blue and analyte-specific MIP) in our perception has a wide scope in that it may be applied to numerous other electroactive species for which specific MIP can be made available.

Graphical Abstract

Prussian blue (PB) and molecularly imprinted polymer (MIP) were combined to fabricate an electrochemical sensor for paracetamol (PR) detection. The ratio of both currents, increase of PR current and decrease of PB current, was employed for PR selective detection with enhanced sensitivity.


Electroanalysis Electropolymerization Paracetamol detection Cyclic voltammetry Differential pulse voltammetry Ratiometric sensor Recognition 



We greatly appreciate the support of the National Natural Science Foundation of China (21575003), Anhui Provincial Natural Science Foundation for Young Program (11040606Q35).

Compliance with ethical standards

The author(s) declare that they have no competing interests.

Supplementary material

604_2016_1926_MOESM1_ESM.doc (506 kb)
ESM 1 Electronic Supplementary Material (DOC 506 kb)


  1. 1.
    Wulff G (2013) Forty years of molecular imprinting in synthetic polymers: Origin, features and perspectives. Microchim Acta 180:1359–1370CrossRefGoogle Scholar
  2. 2.
    Iacob BC, Bodoki E, Florea A (2015) Simultaneous Enantiospecific Recognition of Several β-Blocker Enantiomers Using Molecularly Imprinted Polymer-Based Electrochemical Sensor. Anal Chem 87:2755–2763CrossRefGoogle Scholar
  3. 3.
    Gam-Derrouich BSC, Marcillac WDD, Coolen L, Maitre A, Mangeney C, Schwob C (2015) Quantum dot-imprinted polymers with size and shell-selective recognition properties. Chem Commun 51:14933–14936CrossRefGoogle Scholar
  4. 4.
    Awino JK, Zhao Y (2014) Molecularly imprinted nanoparticles as tailor-made sensors for small fluorescent molecules. Chem Commun 50:5752–5755CrossRefGoogle Scholar
  5. 5.
    Shi HJ, Zhao GH,mailto: Liu MC, Zhu ZL (2011) A novel photoelectrochemical sensor based on molecularly imprinted polymer modified TiO2 nanotubes and its highly selective detection of 2,4-dichlorophenoxyacetic acid. Electrochem Commun 13: 1404–1407Google Scholar
  6. 6.
    N. Karimiana N, Zavarb MHA, Chamsazb M, Turnera APF, Tiwari A (2013) On/off-switchable electrochemical folic acid sensor based on molecularly imprinted polymer electrode. Electrochem Commun 36:92–95CrossRefGoogle Scholar
  7. 7.
    Markas AT (1994) Rapid detection of paracetamol using a disposable, surface-modified screen-printed carbon electrode. Analyst 119:2431–2437CrossRefGoogle Scholar
  8. 8.
    Shiroma LY, Santhiago M, Gobbi AL, Kubota LT (2012) Separation and electrochemical detection of paracetamol and 4-aminophenol in a paper-based microfluidic device. Anal Chim Acta 725:44–50CrossRefGoogle Scholar
  9. 9.
    Santos EDB, Lima ECNL, Oliveira CSD, Sigoli FA, Mazali IO (2014) Fast detection of paracetamol on a gold nanoparticle–chitosan substrate by SERS. Anal Methods 6:3564–3568CrossRefGoogle Scholar
  10. 10.
    Ruiz-Medina A, Córdova MFL, Ayora-Cañada MJ, Pascual-reguera MI, Molina-Díaz A (2000) A flow-through solid phase UV spectrophotometric biparameter sensor for the sequential determination of ascorbic acid and paracetamol. Anal Chim Acta 404:131–139CrossRefGoogle Scholar
  11. 11.
    Easwaramoorthy D, Yu Y-C, Huang H-J (2001) Chemiluminescence detection of paracetamol by a luminol-permanganate based reaction. Anal Chim Acta 439:95–100CrossRefGoogle Scholar
  12. 12.
    Rafael RC, Chaves SC, Ribeiro MMAC, Pascual-reguera MI, Molina-Díaz AJ (2015) Simultaneous determination of caffeine, paracetamol, and ibuprofen in pharmaceutical formulations by high-performance liquid chromatography with UV detection and by capillary electrophoresis with conductivity detection. J Sep Sci 38:1657–1662CrossRefGoogle Scholar
  13. 13.
    Lentini G, Habtemariam S (2014) Microchip capillary electrophoresis–electrospray ionization mass spectrometry analysis of paracetamol metabolites in human urine: An intriguing case. J Chromatogr A 1327:160CrossRefGoogle Scholar
  14. 14.
    Li JH, Liu JL, Tan GG, Jiang JB, Peng SJ, Deng M, Qian D, Feng YL, Liu YC (2014) High-sensitivity paracetamol sensor based on Pd/graphene oxide nanocomposite as an enhanced electrochemical sensing platform. Biosens Bioelectron 54:468–475CrossRefGoogle Scholar
  15. 15.
    Kalambate PK, Sanghavi BJ, Karna SP, Srivastava AK (2015) Simultaneous voltammetric determination of paracetamol and domperidone based on a graphene/platinum nanoparticles/nafion composite modified glassy carbon electrode. Sensors Actuators B Chem 213:285–294CrossRefGoogle Scholar
  16. 16.
    Li L-L, Zhou T-T, Sun GY, Li ZH, Yang WX, Jia JB, Yang GC (2015) Ultrasensitive electrospun nickel-doped carbon nanofibers electrode for sensing paracetamol and glucose. Electrochim Acta 152:31–37CrossRefGoogle Scholar
  17. 17.
    Luo J, Cong J, Fang R, Fei X, Liu X (2014) One-pot synthesis of a graphene oxide coated with an imprinted sol–gel for use in electrochemical sensing of paracetamol. Microchim Acta 181:1257–1266CrossRefGoogle Scholar
  18. 18.
    Liu X, Zhang XY, Wang LL, Wang YY (2014) A sensitive electrochemical sensor for paracetamol based on a glassy carbon electrode modified with multiwalled carbon nanotubes and dopamine nanospheres functionalized with gold nanoparticles. Microchim Acta 181:1439–1446CrossRefGoogle Scholar
  19. 19.
    Teng Y, Fan LM, Dai YL, Zhong M, Lu XJ, Kan XW (2015) Electrochemical sensor for paracetamol recognition and detection based on catalytic and imprinted composite film. Biosens Bioelectron 71:137–142CrossRefGoogle Scholar
  20. 20.
    Liu R, Zeng X, Liu J, Luo J, Zheng Y, Liu X (2016) A glassy carbon electrode modified with an amphiphilic, electroactive and photosensitive polymer and with multi-walled carbon nanotubes for simultaneous determination of dopamine and paracetamol. Microchim Acta 183:1543–1551CrossRefGoogle Scholar
  21. 21.
    Gómez-Caballero A, Goicolea MA, Barrio RJ (2005) Paracetamol voltammetric microsensors based on electrocopolymerized–molecularly imprinted film modified carbon fiber microelectrodes. Analyst 130:1012–1018CrossRefGoogle Scholar
  22. 22.
    Wang CH, Li CY, Wei LF, Wang CF (2007) Electrochemical sensor for acetaminophen based on an imprinted TiO2 thin film prepared by liquid phase deposition. Microchim Acta 158:307–313CrossRefGoogle Scholar
  23. 23.
    Özcan L, Şahin Y (2007) Determination of paracetamol based on electropolymerized-molecularly imprinted polypyrrole modified pencil graphite electrode. Sensors Actuators B Chem 127:362–369CrossRefGoogle Scholar
  24. 24.
    Chuang S-W, Rick J, Chou T-C (2009) Electrochemical characterisation of a conductive polymer molecularly imprinted with an Amadori compound. Biosens Bioelectron 24:3170–3173CrossRefGoogle Scholar
  25. 25.
    Azevado SD, Lakshmi D, Chianella I, Whitcombr MJ, Karim K, Ivanova-Mitseve PK, Subrhmanyam S, Piletsky SA (2013) Molecularly imprinted polymer-hybrid electrochemical sensor for the detection of β-estradiol. Ind Eng Chem Res 52:13917–13923CrossRefGoogle Scholar
  26. 26.
    Huynh T-P, Sosnowska M, Sobczak JW, Chandra BKC, Nesterov VN, D’Souza F, Kutner W (2013) Simultaneous chronoamperometry and piezoelectric microgravimetry determination of nitroaromatic explosives using molecularly imprinted thiophene polymers. Anal Chem 85:8361–8368CrossRefGoogle Scholar
  27. 27.
    Lattach Archirel P, Remita S (2012) Influence of the chemical functionalities of a molecularly imprinted conducting polymer on its sensing properties: electrochemical measurements and semiempirical DFT calculations. J Phys Chem B 116:1467–1481CrossRefGoogle Scholar
  28. 28.
    Karyakin AA (2001) Prussian blue and its analogues: electrochemistry and analytical applications. Electroanalysis 13:813–819CrossRefGoogle Scholar
  29. 29.
    Seeber R, Totir N, Zanardi C (2002) Electrochemical preparation and characterisation of bilayer films composed by Prussian Blue and conducting polymer. Electrochem Commun 4:753–758CrossRefGoogle Scholar
  30. 30.
    Li JP, Li YP, Zhang Y, Wei G (2012) Highly Sensitive Molecularly imprinted electrochemical sensor based on the double amplification by an inorganic Prussian Blue catalytic polymer and the enzymatic effect of glucose oxidase. Anal Chem 84:1888–1893CrossRefGoogle Scholar
  31. 31.
    Li YX, Li YJ, Hong M, Bin Q, Lin ZY, Lin Z, Cai ZW, Chen GN (2013) Highly sensitive protein molecularly imprinted electro-chemical sensor based on gold microdendrites electrode and prussian blue mediatedamplification. Biosens Bioelectron 42:612–617CrossRefGoogle Scholar
  32. 32.
    Cui M, Liu S, Lian WJ, Li J, Xu W, Huang JD (2013) A molecularly-imprinted electrochemical sensor based on a graphene–Prussian blue composite-modified glassy carbon electrode for the detection of butylated hydroxyanisole in foodstuffs. Analyst 138:5949–5955CrossRefGoogle Scholar
  33. 33.
    Yang YK, Cao YY, Wang XM, Fang GZ, Wang S (2015) Prussian blue mediated amplification combined with signal enhancement of ordered mesoporous carbon for ultrasensitive and specific quantification of metolcarb by a three-dimensional molecularly imprinted electrochemical sensor. Biosens Bioelectron 64:247–254CrossRefGoogle Scholar
  34. 34.
    Frasconi M, Tel-Vered R, Riskin M, Willner I (2010) Surface Plasmon resonance analysis of antibiotics using imprinted boronic acid-functionalized Au nanoparticles composites. Anal Chem 82:2512–2519CrossRefGoogle Scholar
  35. 35.
    Rezaei B, Boroujeni MK, Ensafi AA (2015) Fabrication of DNA, o-phenylenediamine, and gold nanoparticle bioimprinted polymer electrochemical sensor for the determination of dopamine. Biosens Bioelectron 66:490–496CrossRefGoogle Scholar
  36. 36.
    Zhong M, Teng Y, Pang S, Yan L, Kan X (2015) pyrrole-phenylboronic acid: a novel monomer for dopamine recognition and detection based on imprinted electrochemical sensor. Biosens Bioelectron 64:212–218CrossRefGoogle Scholar
  37. 37.
    Xia J, Cao X, Wang Z, Yang M, Zhang F, Lu B, Li F, Xia L, Li Y, Xia Y (2016) Molecularly imprinted electrochemical biosensor based on chitosan/ionic liquid-graphene composites modified electrode for determination of bovine serum albumin. Sensors Actuators B Chem 225:305–311CrossRefGoogle Scholar
  38. 38.
    Li BL, Luo JH, Luo HQ, Li NB (2013) A novel strategy for the selective determination of D-penicillamine based on molecularly imprinted polypyrrole electrode via the electrochemical oxidation with ferrocyanide. Sensors Actuators B Chem 186:96–102CrossRefGoogle Scholar
  39. 39.
    Ramanavičius A, Ramanavičienė A, Malinauskas A (2006) Electrochemical sensors based on conducting polymer-pyrrole. Electrochim Acta 51:6025–6037CrossRefGoogle Scholar
  40. 40.
    Suryanarayanan V, Wu C-T, Ho K-C (2010) Molecularly imprinted electrochemical sensors. Electroanalysis 22:1795–1811CrossRefGoogle Scholar
  41. 41.
    Sitnikova NA, Komkova MA, Khomyakova IV, Karyakina EE, Karyakin AA (2014) Transition metal hexacyanoferrates in electrocatalysis of H2O2 reduction: An exclusive property of Prussian Blue. Anal Chem 86:4131–4134CrossRefGoogle Scholar
  42. 42.
    Zhang Y, Sun XM, Zhu LZ, Shen HB, Jia NQ (2011) Electrochemical sensing based on graphene oxide/Prussian blue hybrid film modified electrode. Electrochim Acta 56:1239–1245CrossRefGoogle Scholar
  43. 43.
    Li NB, Park JH, Park K, Kwon JS, Shin H, Kwak J (2008) Characterization and electrocatalytic properties of Prussian blue electrochemically deposited on nano-Au/PAMAM dendrimer-modified gold electrode. Biosens Bioelectron 23:1519–1526CrossRefGoogle Scholar
  44. 44.
    Ricci F, Goncalves C, Amine A, Gorton L, Palleschi G, Moscone D (2003) Electroanalytical study of Prussian Blue modified glassy carbon paste electrodes. Electroanalysis 15:1204–1211CrossRefGoogle Scholar
  45. 45.
    Jiang YY, Zhang XD, Shan CS, Hua SC, Zhang QX, Bai XX, Dan L, Niu L (2011) Functionalization of graphene with electrodeposited Prussian blue towards amperometric sensing application. Talanta 85:76–81CrossRefGoogle Scholar
  46. 46.
    Adhikari B-R, Govindhan M, Chen A (2015) Sensitive Detection of acetaminophen with graphene-based electrochemical sensor. Electrochim Acta 162:198–204CrossRefGoogle Scholar
  47. 47.
    Mao AR, Li HB, Jin DQ, Yu LY, Hu XY (2015) Fabrication of electrochemical sensor for paracetamol based on multi-walled carbon nanotubes and chitosan–copper complex by self-assembly technique. Tanalta 144:252–257Google Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Yunlong Dai
    • 1
    • 2
  • Xueyan Li
    • 1
    • 2
  • Xiaojing Lu
    • 1
    • 2
  • Xianwen Kan
    • 1
    • 2
    Email author
  1. 1.College of Chemistry and Materials ScienceAnhui Normal UniversityWuhuPeople’s Republic of China
  2. 2.The Key Laboratory of Functional Molecular Solids, Ministry of Education; Anhui Laboratory of Molecule-Based Materials, Anhui Key Laboratory of Chemo-BiosensingAnhui Normal UniversityWuhuPeople’s Republic of China

Personalised recommendations