, Volume 24, Issue 3, pp 833–843 | Cite as

Determination of tramadol in pharmaceutical products and biological samples using a new nanocomposite carbon paste sensor based on decorated nanographene/tramadol-imprinted polymer nanoparticles/ionic liquid

  • Hasan Bagheri
  • Ali Shirzadmehr
  • Mosayeb Rezaei
  • Hosein Khoshsafar
Original Paper


In the present research, design and construction of a development potentiometric sensor based on a newly nanosensing layer for the sensitive determination of tramadol in various real samples were suggested. The proposed nanosensing layer was fabricated with the incorporation of a synthesized tramadol-imprinted polymer nanoparticles “as an efficient sensing agent” into the carbon paste matrix composed of graphite powder, decorated graphene nanosheets with silver nanoparticles, and a typically ionic liquid as the conductive pasting binder. The detection limit and the linear range of this study were found to be 2.04 × 10−9 and 3.50 × 10−9 to 1.00 × 10−2 M with a Nernstian slope of 59.85 ± 0.13 mV decade−1, respectively. The presented modified carbon paste sensor was successfully applied for the determination of tramadol in pharmaceutical and biological samples.


Tramadol-imprinted polymer Potentiometric sensor Decorated nanographene Silver nanoparticles Ionic liquid 



The authors wish to thank the Young Researchers and Elite Club at the Islamic Azad University, Iran. And also, the authors thank the Researches and Technology Council, Baqiyatallah University of Medical Sciences, Tehran, Iran, for the support.


  1. 1.
    Ganjali MR, Larijani B, Pourbasheer E (2016) Fabrication of an all solid state (ASS) polymeric membrane sensor (PME) for tramadol and its application. Int J Electrochem Sci 11:2119–2129Google Scholar
  2. 2.
    Bagheri H, Afkhami A, Panahi Y, Khoshsafar H, Shirzadmehr A (2014) Facile stripping voltammetric determination of haloperidol using a high performance magnetite/carbon nanotube paste electrode in pharmaceutical and biological samples. Mater Sci Eng C 37:264–270CrossRefGoogle Scholar
  3. 3.
    Afkhami A, Shirzadmehr A, Madrakian T (2014) Improvement in performance of a hyoscine butylbromide potentiometric sensor using a new nanocomposite carbon paste: a comparison study with polymeric membrane sensor. Ionics 20:1145–1154CrossRefGoogle Scholar
  4. 4.
    Bagheri H, Shirzadmehr A, Rezaei M (2015) Designing and fabrication of new molecularly imprinted polymer-based potentiometric nano-graphene/ionic liquid/carbon paste electrode for the determination of losartan. J Mol Liq 212:96–102CrossRefGoogle Scholar
  5. 5.
    Khoshsafar H, Bagheri H, Rezaei M, Shirzadmehr A, Hajian A, Sepehri Z (2016) Magnetic carbon paste electrode modified with a high performance composite based on molecularly imprinted carbon nanotubes for sensitive determination of levofloxacin. J Electrochem Soc 163:B422–B427CrossRefGoogle Scholar
  6. 6.
    Fouladgar M, Karimi-Maleh H (2013) Ionic liquid/multiwall carbon nanotubes paste electrode for square wave voltammetric determination of methyldopa. Ionics 19:1163–1170CrossRefGoogle Scholar
  7. 7.
    Beitollahi H, Mohadesi A, Mostafavi M, Karimi-Maleh H, Baghayeri M, Akbari A (2014) Voltammetric sensor for simultaneous determination of ascorbic acid, acetaminophen, and tryptophan in pharmaceutical products. Ionics 20:729–737CrossRefGoogle Scholar
  8. 8.
    Leppert W (2009) Tramadol as an analgesic for mild to moderate cancer pain. Pharmacol Rep 61:978–992CrossRefGoogle Scholar
  9. 9.
    Shadnia S, Soltaninejad K, Heydari K, Sasanian G, Abdollahi M (2008) Tramadol intoxication: a review of 114 cases. Hum Exp Toxicol 27:201–205CrossRefGoogle Scholar
  10. 10.
    Marquardt KA, Alsop JA, Albertson TE (2005) Tramadol exposures reported to statewide poison control system. Ann Pharmacother 39:1039–1044CrossRefGoogle Scholar
  11. 11.
    Mugunthan N, Davoren P (2012) Danger of hypoglycemia due to acute tramadol poisoning. Endocr Pract 18:e151–e152CrossRefGoogle Scholar
  12. 12.
    Taghaddosinejad F, Mehrpour O, Afshari R, Seghatoleslami A, Abdollahi M, Dart RC (2011) Factors related to seizure in tramadol poisoning and its blood concentration. J Med Toxicol 7:183–188CrossRefGoogle Scholar
  13. 13.
    Rúa-Gómez PC, Püttmann W (2012) Occurrence and removal of lidocaine, tramadol, venlafaxine, and their metabolites in German wastewater treatment plants. Environ Sci Pollut Res 19:689–699CrossRefGoogle Scholar
  14. 14.
    Ardakani YH, Foroumadi RA, Rouini MR (2008) Enantioselective determination of tramadol and its main phase I metabolites in human plasma by high-performance liquid chromatography. J Chromatogr B 864:109–115CrossRefGoogle Scholar
  15. 15.
    Campanero MA, Garcia-Quetglas E, Sadaba B, Azanza JR (2004) Simultaneous stereoselective analysis of tramadol and its primary phase I metabolites in plasma by liquid chromatography: application to a pharmacokinetic study in humans. J Chromatogr A 1031:219–228CrossRefGoogle Scholar
  16. 16.
    Gu Y, Fawcett JP (2005) Improved HPLC method for the simultaneous determination of tramadol and O-desmethyltramadol in human plasma. J Chromatogr B 821:240–243CrossRefGoogle Scholar
  17. 17.
    Musshoff F, Madea B, Stuber F, Stamer UM (2006) Enantiomeric determination of tramadol and O-desmethyltramadol by liquid chromatography-mass spectrometry and application to postoperative patients receiving tramadol. J Anal Toxicol 30:463–467CrossRefGoogle Scholar
  18. 18.
    Sha YF, Shen S, Duan GL (2005) Rapid determination of tramadol in human plasma by headspace solid-phase microextraction and capillary gas chromatography–mass spectrometry. J Pharmaceut Biomed Anal 37:143–147CrossRefGoogle Scholar
  19. 19.
    Leis HJ, Fauler G, Windischhofer W (2004) Synthesis of d1-N-ethyltramadol as an internal standard for the quantitative determination of tramadol in human plasma by gas chromatography–mass spectrometry. J Chromatogr B 804:369–374CrossRefGoogle Scholar
  20. 20.
    Gambaro V, Benvenuti C, De Ferrari L, Dell’Acqua L, Farè F (2003) Validation of a GC/MS method for the determination of tramadol in human plasma after intravenous bolus. Il Farmaco 58:947–950CrossRefGoogle Scholar
  21. 21.
    Li J, Ju H (2006) Simultaneous determination of ethamsylate, tramadol and lidocaine in human urine by capillary electrophoresis with electrochemiluminescence detection. Electrophoresis 27:3467–3474CrossRefGoogle Scholar
  22. 22.
    Flores JR, Nevado JJB, Salcedo AMC, Diaz MPC (2004) Development of capillary zone electrophoretic method to determine six antidepressants in their pharmaceutical preparations experimental design for evaluating the ruggedness of method. J Sep Sci 27:33–40CrossRefGoogle Scholar
  23. 23.
    Abdellatef HE (2002) Kinetic spectrophotometric determination of tramadol hydrochloride in pharmaceutical formulation. J Pharm Biomed Anal 29:835–842CrossRefGoogle Scholar
  24. 24.
    Nobilis M, Pastera J, Anzenbacher P, Svoboda D, Kopecky J, Perlik F (1996) High-performance liquid chromatographic determination of tramadol in human plasma. J Chromatogr B 681:177–183CrossRefGoogle Scholar
  25. 25.
    Ebrahimzadeh H, Tamini Y, Sedighi A, Rouini MR (2008) Determination of tramadol in human plasma and urine samples using liquid phase microextraction with back extraction combined with high performance liquid chromatography. J Chromatogr B 863:229–234CrossRefGoogle Scholar
  26. 26.
    Afkhami A, Ghaedi H, Madrakian T, Ahmadi M, Mahmood-Kashani H (2013) Fabrication of a new electrochemical sensor based on a new nano-molecularly imprinted polymer for highly selective and sensitive determination of tramadol in human urine samples. Biosens Bioelectron 44:34–40CrossRefGoogle Scholar
  27. 27.
    Afkhami A, Khoshsafar H, Bagheri H, Madrakian T (2014) Preparation of NiFe2O4/graphene nanocomposite and its application as a modifier for the fabrication of an electrochemical sensor for the simultaneous determination of tramadol and acetaminophen. Anal Chim Acta 831:50–59CrossRefGoogle Scholar
  28. 28.
    Abbastabar-Ahangar H, Shirzadmehr A, Marjani K, Khoshsafar H, Chaloosi M, Mohammadi L (2009) Ion-selective carbon paste electrode based on new tripodal ligand for determination of cadmium (II). J Incl Phenom Macrocycl Chem 63:287–293CrossRefGoogle Scholar
  29. 29.
    Ganjali MR, Khoshsafar H, Faridbod F, Shirzadmehr A, Javanbakht M, Norouzi P (2009) Room temperature ionic liquids (RTILs) and multiwalled carbon nanotubes (MWCNTs) as modifiers for improvement of carbon paste ion selective electrode response; a comparison study with PVC membrane. Electroanalysis 21:2175–2178CrossRefGoogle Scholar
  30. 30.
    Ganjali MR, Khoshsafar H, Shirzadmehr A, Javanbakht M, Faridbod F (2009) Improvement of carbon paste ion selective electrode response by using room temperature ionic liquids (RTILs) and multi-walled carbon nanotubes (MWCNTs). Int J Electrochem Sci 4:435–443Google Scholar
  31. 31.
    Afkhami A, Madrakian T, Shirzadmehr A, Bagheri H, Tabatabaee M (2012) A selective sensor for nanolevel detection of lead (II) in hazardous wastes using ionic-liquid/Schiff base/MWCNTs/nanosilica as a highly sensitive composite. Ionics 18:881–889CrossRefGoogle Scholar
  32. 32.
    Bagheri H, Afkhami A, Shirzadmehr A, Khoshsafar H (2014) A new nano-composite modified carbon paste electrode as a high performance potentiometric sensor for nanomolar Tl(I) determination. J Mol Liq 197:52–57CrossRefGoogle Scholar
  33. 33.
    Afkhami A, Madrakian T, Shirzadmehr A, Tabatabaee M, Bagheri H (2012) New Schiff base-carbon nanotube–nanosilica–ionic liquid as a high performance sensing material of a potentiometric sensor for nanomolar determination of cerium(III) ions. Sens Actuators B Chem 174:237–244CrossRefGoogle Scholar
  34. 34.
    Bagheri H, Afkhami A, Saber-Tehrani M, Shirzadmehr A, Husain SW, Khoshsafar H, Tabatabaee M (2012) Novel sensor fabrication for the determination of nanomolar concentrations of Ce3+ in aqueous solutions. Anal Methods 4:1753–1758CrossRefGoogle Scholar
  35. 35.
    Afkhami A, Bagheri H, Shirzadmehr A, Khoshsafar H, Hashemi P (2012) A potentiometric sensor for Cd2+ based on carbon nanotube paste electrode constructed from room temperature ionic liquid, ionophore and silica nanoparticles. Electroanalysis 24:2176–2185CrossRefGoogle Scholar
  36. 36.
    Bagheri H, Afkhami A, Shirzadmehr A, Khoshsafar H, Khoshsafar H, Ghaedi H (2013) Novel potentiometric sensor for the determination of Cd2+ based on a new nano-composite. Intern J Environ Anal Chem 93:578–591CrossRefGoogle Scholar
  37. 37.
    Afkhami A, Shirzadmehr A, Madrakian T, Bagheri H (2014) Improvement in the performance of a Pb2+ selective potentiometric sensor using modified core/shell SiO2/Fe3O4 nano-structure. J Mol Liq 199:108–114CrossRefGoogle Scholar
  38. 38.
    Afkhami A, Khoshsafar H, Madrakian T, Shirzadmehr A (2014) A new nano-composite electrode as a copper (II) selective potentiometric sensor. J Iran Chem Soc 11:1373–1380CrossRefGoogle Scholar
  39. 39.
    Afkhami A, Shirzadmehr A, Madrakian T, Bagheri H (2015) New nano-composite potentiometric sensor composed of graphene nanosheets/thionine/molecular wire for nanomolar detection of silver ion in various real samples. Talanta 131:548–555CrossRefGoogle Scholar
  40. 40.
    Shirzadmehr A, Afkhami A, Madrakian T (2015) A new nano-composite potentiometric sensor containing an Hg2+-ion imprinted polymer for the trace determination of mercury ions in different matrices. J Mol Liq 204:227–235CrossRefGoogle Scholar
  41. 41.
    Bagheri H, Shirzadmehr A, Rezaei M (2016) Determination of copper ions in foodstuff products with a newly modified potentiometric carbon paste electrode based on a novel nano-sensing layer. Ionics 22:1241–1252CrossRefGoogle Scholar
  42. 42.
    Shirzadmehr A, Rezaei M, Bagheri H, Khoshsafar H (2016) Novel potentiometric sensor for the trace level determination of Zn2+ based on a new nanographene/ion imprinted polymer composite. Intern J Environ Anal Chem 96:929–944CrossRefGoogle Scholar
  43. 43.
    Soleimani M, Ghaderi S, Ghahraman Afshar M, Soleimani S (2012) Synthesis of molecularly imprinted polymer as a sorbent for solid phase extraction of bovine albumin from whey, milk, urine and serum. Microchem J 100:1–7CrossRefGoogle Scholar
  44. 44.
    Hirata M, Gotou T, Horiuchi S, Fujiwara M, Ohba M (2004) Thin-film particles of graphite oxide 1: High-yield synthesis and flexibility of the particles. Carbon 42:2929–2937Google Scholar
  45. 45.
    Hummers WS, Offeman RE (1958) Preparation of graphitic oxide. J Am Chem Soc 80:1339–1339CrossRefGoogle Scholar
  46. 46.
    Tien HW, Huang YL, Yang SY, Wang JY, Ma CCM (2011) The production of graphene nanosheets decorated with silver nanoparticles for use in transparent, conductive films. Carbon 49:1550–1560CrossRefGoogle Scholar
  47. 47.
    Seifi M, Hassanpour Moghadam M, Hadizadeh F, Ali-Asgari S, Aboli J, Mohajeri SA (2014) Preparation and study of tramadol imprinted micro-and nanoparticles by precipitation polymerization: microwave irradiation and conventional heating method. Int J Pharm 471:37–44CrossRefGoogle Scholar
  48. 48.
    Khani H, Rofouei MK, Arab P, Gupta VK, Vafaei Z (2010) Multi-walled carbon nanotubes-ionic liquid-carbon paste electrode as a super selectivity sensor: application to potentiometric monitoring of mercury ion(II). J Hazard Mater 183:402–409CrossRefGoogle Scholar
  49. 49.
    Abu-Shawish HM, Abu Ghalwa N, Zaggout FR, Saadeh SM, Al-Dalou AR, Abou Assi AA (2010) Improved determination of tramadol hydrochloride in biological fluids and pharmaceutical preparations utilizing a modified carbon paste electrode. Biochem Eng J 48:237–245CrossRefGoogle Scholar
  50. 50.
    Abu Shawish HM, Saadeh SM, Al-Dalou AR, Abu Ghalwa N, Abou Assi AA (2011) Optimization of tramadol–PVC membrane electrodes using miscellaneous plasticizers and ion-pair complexes. Mater Sci Eng C 31:300–306CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Hasan Bagheri
    • 1
  • Ali Shirzadmehr
    • 2
  • Mosayeb Rezaei
    • 3
  • Hosein Khoshsafar
    • 3
  1. 1.Chemical Injuries Research CenterBaqiyatallah University of Medical SciencesTehranIran
  2. 2.Young Researchers and Elite Club, Sari BranchIslamic Azad UniversitySariIran
  3. 3.Young Researchers and Elite Club, Hamedan BranchIslamic Azad UniversityHamedanIran

Personalised recommendations