Skip to main content
SpringerLink
Log in

All solid-state miniaturized potentiometric sensors for flunitrazepam determination in beverages

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract

Flunitrazepam is one of the frequently used hypnotic drugs to incapacitate victims for sexual assault. Appropriate diagnostic tools should be available to victims regarding the growing concern about “date-rape drugs” and their adverse impact on society. Miniaturized screen-printed potentiometric sensors offer crucial point-of-care devices that alleviate this serious problem. In this study, all solid-state screen-printed potentiometric flunitrazepam sensors have been designed. The paper device was printed with silver and carbon ink. Formation of an aqueous layer in the interface between carbon-conducting material and ion-sensing membrane nevertheless poses low reproducibility in the solid-contact electrodes. Accordingly, poly(3,4-ethylenedioxythiophene) (PEDT) nano-dispersion was applied as a conducting hydrophobic polymer on the electrode surface to curb water accumulation. Conditioning of ion-sensing membrane in the vicinity of reference membrane has been considered carefully using special protocol. Electrochemical characteristics of the proposed PEDT-based sensor were calculated and compared favorably to PEDT-free one. The miniaturized device was successfully used for the determination of flunitrazepam in carbonated soft drinks, energy drink, and malt beverage. Statistical comparison between the proposed sensor and official method revealed no significant difference. Nevertheless, the proposed sensor provides simple and user-friendly diagnostic tool with less equipment for on-site determination of flunitrazepam.

Graphical abstract

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

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. Mattila M, Larni H (1980) Flunitrazepam: a review of its pharmacological properties and therapeutic use. Drugs 20(5):353–374. https://doi.org/10.2165/00003495-198020050-00002

    Article  CAS  PubMed  Google Scholar 

  2. Simmons MM, Cupp MJ (1998) Use and abuse of flunitrazepam. Ann Pharmacother 32(1):117–119. https://doi.org/10.1345/aph.17027

    Article  CAS  PubMed  Google Scholar 

  3. Kehner GB, Triggle DJ (2009) Date Rape Drugs. Infobase Publishing, New York

    Google Scholar 

  4. Emmett D, Nice G (2005) Understanding street drugs: a handbook of substance misuse for parents. Jessica Kingsley Publishers, Philadelphia

    Google Scholar 

  5. Smith KM, Larive LL, Romanelli F (2002) Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate. Am J Health Syst Pharm 59(11):1067–1076. https://doi.org/10.1093/ajhp/59.11.1067

    Article  CAS  PubMed  Google Scholar 

  6. Schwartz RH, Milteer R, LeBeau MA (2000) Drug-facilitated sexual assault (‘date rape’). South Med J 93(6):558–561. https://doi.org/10.1097/00007611-200093060-00002

    Article  CAS  PubMed  Google Scholar 

  7. Brown SD, Melton TC (2011) Trends in bioanalytical methods for the determination and quantification of club drugs: 2000–2010. Biomed Chromatogr 25(1–2):300–321. https://doi.org/10.1002/bmc.1549

    Article  CAS  PubMed  Google Scholar 

  8. Magrini L, Cappiello A, Famiglini G, Palma P (2016) Microextraction by packed sorbent (MEPS)-UHPLC-UV: a simple and efficient method for the determination of five benzodiazepines in an alcoholic beverage. J Pharm Biomed Anal 125:48–53. https://doi.org/10.1016/j.jpba.2016.03.028

    Article  CAS  PubMed  Google Scholar 

  9. Famiglini G, Termopoli V, Palma P, Cappiello A (2016) Liquid chromatography-electron ionization tandem mass spectrometry with the Direct-EI interface in the fast determination of diazepam and flunitrazepam in alcoholic beverages. Electrophoresis 37(7–8):1048–1054. https://doi.org/10.1002/elps.201500517

    Article  CAS  PubMed  Google Scholar 

  10. Honeychurch KC, Davidson GM, Brown E, Hart JP (2015) Novel reductive–reductive mode electrochemical detection of Rohypnol following liquid chromatography and its determination in coffee. Anal Chim Acta 853:222–227. https://doi.org/10.1016/j.aca.2014.09.033

    Article  CAS  PubMed  Google Scholar 

  11. Sabia R, Ciogli A, Pierini M, Gasparrini F, Villani C (2014) Dynamic high performance liquid chromatography on chiral stationary phases. Low temperature separation of the interconverting enantiomers of diazepam, flunitrazepam, prazepam and tetrazepam. J Chromatogr A 1363:144–149. https://doi.org/10.1016/j.chroma.2014.07.097

    Article  CAS  PubMed  Google Scholar 

  12. Lee HH, Lee JF, Lin SY, Lin YY, Wu CF, Wu MT, Chen BH (2013) Simultaneous quantification of urine flunitrazepam, nimetazepam and nitrazepam by using liquid chromatography tandem mass spectrometry. Clin Chim Acta 420:134–139. https://doi.org/10.1016/j.cca.2012.10.023

    Article  CAS  PubMed  Google Scholar 

  13. Lendoiro E, Quintela Ó, de Castro A, Cruz A, López-Rivadulla M, Concheiro M (2012) Target screening and confirmation of 35 licit and illicit drugs and metabolites in hair by LC–MSMS. Forensic Sci Int 217(1–3):207–215. https://doi.org/10.1016/j.forsciint.2011.11.006

    Article  CAS  PubMed  Google Scholar 

  14. Kiss B, Bogdan C, Pop A, Loghin F (2012) A rapid UPLC–MS/MS method for simultaneous determination of flunitrazepam, 7-aminoflunitrazepam, methadone and EDDP in human, rat and rabbit plasma. Talanta 99:649–659. https://doi.org/10.1016/j.talanta.2012.06.070

    Article  CAS  PubMed  Google Scholar 

  15. Ali EM, Edwards HG (2017) The detection of flunitrazepam in beverages using portable Raman spectroscopy. Drug Test Anal 9(2):256–259. https://doi.org/10.1002/dta.1969

    Article  CAS  PubMed  Google Scholar 

  16. D'Aloise P, Chen H (2012) Rapid determination of flunitrazepam in alcoholic beverages by desorption electrospray ionization-mass spectrometry. Sci Justice 52(1):2–8. https://doi.org/10.1016/j.scijus.2011.08.007

    Article  CAS  PubMed  Google Scholar 

  17. Yen Y-T, Lin Y-S, Chen T-H, Chyueh S-C, Chang H-T (2020) A carbon-dot sensing probe for screening of date rape drugs: nitro-containing benzodiazepines. Sensors Actuators B Chem 305:127441. https://doi.org/10.1016/j.snb.2019.127441

    Article  CAS  Google Scholar 

  18. Garcia-Gutierrez E, Lledo-Fernandez C (2013) Electroanalytical sensing of flunitrazepam based on screen printed graphene electrodes. Chemosensors 1(3):68–77. https://doi.org/10.3390/chemosensors1030068

    Article  Google Scholar 

  19. Smith JP, Metters JP, Kampouris DK, Lledo-Fernandez C, Sutcliffe OB, Banks CE (2013) Forensic electrochemistry: the electroanalytical sensing of Rohypnol®(flunitrazepam) using screen-printed graphite electrodes without recourse for electrode or sample pre-treatment. Analyst 138(20):6185–6191. https://doi.org/10.1039/C3AN01352A

    Article  CAS  PubMed  Google Scholar 

  20. Tseliou F, Pappas P, Spyrou K, Hrbac J, Prodromidis MI (2019) Lab-on-a-screen-printed electrochemical cell for drop-volume voltammetric screening of flunitrazepam in untreated, undiluted alcoholic and soft drinks. Biosens Bioelectron 132:136–142. https://doi.org/10.1016/j.bios.2019.03.001

    Article  CAS  PubMed  Google Scholar 

  21. Sohouli E, Ghalkhani M, Rostami M, Rahimi-Nasrabadi M, Ahmadi F (2020) A noble electrochemical sensor based on TiO2@CuO-N-rGO and poly (L-cysteine) nanocomposite applicable for trace analysis of flunitrazepam. Mater Sci Eng C 117:111300. https://doi.org/10.1016/j.msec.2020.111300

    Article  CAS  Google Scholar 

  22. Ghanbari MH, Norouzi Z, Ghanbari MM (2020) Using a nanocomposite consist of Boron-doped reduced graphene oxide and electropolymerized β-cyclodextrin for flunitrazepam electrochemical sensor. Microchem J 156:104994. https://doi.org/10.1016/j.microc.2020.104994

    Article  CAS  Google Scholar 

  23. Asiabar BM, Karimi MA, Tavallali H, Rahimi-Nasrabadi M (2021) Application of MnFe2O4 and AuNPs modified CPE as a sensitive flunitrazepam electrochemical sensor. Microchem J 161:105745. https://doi.org/10.1016/j.microc.2020.105745

    Article  CAS  Google Scholar 

  24. Harper L, Powell J, Pijl EM (2017) An overview of forensic drug testing methods and their suitability for harm reduction point-of-care services. Harm Reduct J 14(1):52. https://doi.org/10.1186/s12954-017-0179-5

    Article  PubMed  PubMed Central  Google Scholar 

  25. Fawaz EM, El-Rahman MKA, Riad SM, Shehata MA (2018) Screen printed ion selective electrodes as a fully integrated PAT tool: application to the analysis and impurity profiling of diatrizoate sodium. J Electrochem Soc 165(7):B323–B327. https://doi.org/10.1149/2.1311807jes

    Article  CAS  Google Scholar 

  26. Mohamed HM (2016) Screen-printed disposable electrodes: pharmaceutical applications and recent developments. TrAC Trends Anal Chem 82:1–11. https://doi.org/10.1016/j.trac.2016.02.010

    Article  CAS  Google Scholar 

  27. Yehia AM, Saad AS, Tantawy MA (2020) USB multiplex analyzer employing screen-printed silver electrodes on paper substrate; a developed design for dissolution testing. J Pharm Biomed Anal 186:113272. https://doi.org/10.1016/j.jpba.2020.113272

    Article  CAS  PubMed  Google Scholar 

  28. Bakker E, Pretsch E (2005) Potentiometric sensors for trace-level analysis. TrAC Trends Anal Chem 24(3):199–207. https://doi.org/10.1016/j.trac.2005.01.003

    Article  CAS  Google Scholar 

  29. Mahmoud AT, Haitham AEF, Amr MB, Maha FAEG, Fares NV (2021) A novel glassy carbon electrode modified with multi-walled carbon nanotubes for potentiometric xipamide determination. J Electrochem Soc 168:056506. https://doi.org/10.1149/1945-7111/abfcdb

    Article  Google Scholar 

  30. Bobacka J (1999) Potential stability of all-solid-state ion-selective electrodes using conducting polymers as ion-to-electron transducers. Anal Chem 71(21):4932–4937. https://doi.org/10.1021/ac990497z

    Article  CAS  PubMed  Google Scholar 

  31. Michalska A (2006) Optimizing the analytical performance and construction of ion-selective electrodes with conducting polymer-based ion-to-electron transducers. Anal Bioanal Chem 384(2):391–406. https://doi.org/10.1007/s00216-005-0132-4

    Article  CAS  PubMed  Google Scholar 

  32. El-Rahman MKA, Rezk MR, Mahmoud AM, Elghobashy MR (2015) Design of a stable solid-contact ion-selective electrode based on polyaniline nanoparticles as ion-to-electron transducer for application in process analytical technology as a real-time analyzer. Sensors Actuators B Chem 208:14–21. https://doi.org/10.1016/j.snb.2014.11.009

    Article  CAS  Google Scholar 

  33. Yehia AM, Farag MA, Tantawy MA (2020) A novel trimodal system on a paper-based microfluidic device for on-site detection of the date rape drug “ketamine”. Anal Chim Acta 1104:95–104. https://doi.org/10.1016/j.aca.2020.01.002

    Article  CAS  PubMed  Google Scholar 

  34. Bobacka J, Ivaska A, Lewenstam A (2008) Potentiometric ion sensors. Chem Rev 108(2):329–351. https://doi.org/10.1021/cr068100w

    Article  CAS  PubMed  Google Scholar 

  35. Kirchmeyer S, Reuter K (2005) Scientific importance, properties and growing applications of poly (3, 4-ethylenedioxythiophene). J Mater Chem 15(21):2077–2088. https://doi.org/10.1039/B417803N

    Article  CAS  Google Scholar 

  36. Boehler C, Aqrawe Z, Asplund M (2019) Applications of PEDOT in bioelectronic medicine. Bioelectronics in Medicine 2(2):89–99. https://doi.org/10.2217/bem-2019-0014

    Article  Google Scholar 

  37. British Pharmacopeia (2013) In, vol I. The Stationary Office, London, p 660

  38. Hu L, Wu H, Cui Y (2010) Printed energy storage devices by integration of electrodes and separators into single sheets of paper. Appl Phys Lett 96(18):183502. https://doi.org/10.1063/1.3425767

    Article  CAS  Google Scholar 

  39. Mattinen U, Bobacka J, Lewenstam A (2009) Solid-contact reference electrodes based on lipophilic salts. Electroanalysis 21(17–18):1955–1960. https://doi.org/10.1002/elan.200904615

    Article  CAS  Google Scholar 

  40. Rich M, Mendecki L, Mensah ST, Blanco-Martinez E, Armas S, Calvo-Marzal P, Radu A, Chumbimuni-Torres KY (2016) Circumventing traditional conditioning protocols in polymer membrane-based ion-selective electrodes. Anal Chem 88(17):8404–8408. https://doi.org/10.1021/acs.analchem.6b01542

    Article  CAS  PubMed  Google Scholar 

  41. Bakker E, Pretsch E, Bühlmann P (2000) Selectivity of potentiometric ion sensors. Anal Chem 72(6):1127–1133. https://doi.org/10.1021/ac991146n

    Article  CAS  PubMed  Google Scholar 

  42. Gupta VK, Goyal RN, Sharma RA (2009) Comparative studies of neodymium (III)-selective PVC membrane sensors. Anal Chim Acta 647(1):66–71. https://doi.org/10.1016/j.aca.2009.05.031

    Article  CAS  PubMed  Google Scholar 

  43. Yehia AM, Abo-Elhoda SE, Hassan NY, Badawey AM (2018) Experimental validation of a computationally-designed tiotropium membrane sensor. New J Chem 42(19):16354–16361. https://doi.org/10.1039/C8NJ03507E

    Article  CAS  Google Scholar 

  44. Gupta VK, Kumar S, Singh R, Singh LP, Shoora SK, Sethi B (2014) Cadmium (II) ion sensing through p-tert-butyl calix[6]arene based potentiometric sensor. J Mol Liq 195:65–68. https://doi.org/10.1016/j.molliq.2014.02.001

    Article  CAS  Google Scholar 

  45. Lenik J, Nieszporek J (2018) Construction of a glassy carbon ibuprofen electrode modified with multi-walled carbon nanotubes and cyclodextrins. Sensors Actuators B Chem 255:2282–2289. https://doi.org/10.1016/j.snb.2017.09.034

    Article  CAS  Google Scholar 

  46. De Marco R, Veder J-P, Clarke G, Nelson A, Prince K, Pretsch E, Bakker E (2008) Evidence of a water layer in solid-contact polymeric ion sensors. Phys Chem Chem Phys 10(1):73–76. https://doi.org/10.1039/B714248J

    Article  PubMed  Google Scholar 

  47. Buck RP, Lindner E (1994) Recommendations for nomenclature of ionselective electrodes (IUPAC Recommendations 1994). Pure Appl Chem 66(12):2527–2536. https://doi.org/10.1351/pac199466122527

    Article  CAS  Google Scholar 

  48. Sutter J, Radu A, Peper S, Bakker E, Pretsch E (2004) Solid-contact polymeric membrane electrodes with detection limits in the subnanomolar range. Anal Chim Acta 523(1):53–59. https://doi.org/10.1016/j.aca.2004.07.016

    Article  CAS  Google Scholar 

  49. Thomas AG, Muniandy K (1987) Absorption and desorption of water in rubbers. Polymer 28(3):408–415. https://doi.org/10.1016/0032-3861(87)90193-5

    Article  CAS  Google Scholar 

  50. Li Z, Li X, Petrović S, Harrison DJ (1996) Dual-sorption model of water uptake in poly(vinyl chloride)-based ion-selective membranes: experimental water concentration and transport parameters. Anal Chem 68(10):1717–1725. https://doi.org/10.1021/ac950557a

    Article  CAS  Google Scholar 

  51. Veder J-P, De Marco R, Clarke G, Chester R, Nelson A, Prince K, Pretsch E, Bakker E (2008) Elimination of undesirable water layers in solid-contact polymeric ion-selective electrodes. Anal Chem 80(17):6731–6740. https://doi.org/10.1021/ac800823f

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. ten Brink B, Damink C, Joosten HMLJ, Huis in 't Veld JHJ (1990) Occurrence and formation of biologically active amines in foods. Int J Food Microbiol 11(1):73–84. https://doi.org/10.1016/0168-1605(90)90040-C

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the funding received from the Young Investigator Research Grants (YIRG) hosted by the British University in Egypt.

Author information

Authors and Affiliations

  1. Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, El-Kasr El-Aini Street, Cairo, 11562, Egypt

    Mahmoud A. Tantawy & Ali M. Yehia

  2. Chemistry Department, Faculty of Pharmacy, October 6 University, 6 October City, Giza, Egypt

    Mahmoud A. Tantawy

  3. Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El Sherouk City, Cairo, 11837, Egypt

    Ekram H. Mohamed

  4. School of Life and Medical Sciences, University of Hertfordshire Hosted By Global Academic Foundation, R5 New Garden City, New Capital, Cairo, Egypt

    Ali M. Yehia

Authors
  1. Mahmoud A. Tantawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ekram H. Mohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ali M. Yehia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali M. Yehia.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interest.

Additional information

Publisher’s note

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

Supplementary information

ESM 1

(DOCX 810 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tantawy, M.A., Mohamed, E.H. & Yehia, A.M. All solid-state miniaturized potentiometric sensors for flunitrazepam determination in beverages. Microchim Acta 188, 192 (2021). https://doi.org/10.1007/s00604-021-04851-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-021-04851-9

Keywords

Search

Navigation