Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Polyacrylonitrile/MIL-53(Fe) electrospun nanofiber for pipette-tip micro solid phase extraction of nitrazepam and oxazepam followed by HPLC analysis

  • 63 Accesses


Nanofibers were prepared from a nanocomposite consisting of polyacrylonitrile and a metal-organic framework of type MIL-53(Fe) by electrospinning. They are shown to be a viable sorbent for pipette-tip solid-phase extraction for the extraction of the benzodiazepine drugs nitrazepam and oxazepam. The nanofibers were characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy and X-ray diffraction. The effects of sample pH value and volume, composition, and amount of electrospun nanofibers, the number of adsorption cycles and the type and volume of the eluent were optimized. Following extraction the drugs were quantified by HPLC. Under the optimized conditions, response is linear for both drugs in the 5.0–1000 ng mL−1 concentration range. The limits of detection for oxazepam and nitrazepam are 1.5 and 2.5 ng mL−1, respectively, and the relative standard deviations at the levels of 50, 100 and 250 ng mL−1 (for n = 3) are ≤7.6%. The method was successfully applied for determination of drugs in spiked wastewater and biological fluids.

Schematic representation of polyacrylonitrile/MIL-53(Fe) composite nanofiber synthesis by electrospinning, and the use of them as the sorbent in pipette-tip microsolid-phase extraction (PT–μSPE) for the preconcentration of Nitrazepam and Oxazepam before HPLC–DAD analysis.

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

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Alizadeh R, Salami M, Seidi S (2018) A silica fiber coated with a ZnO-graphene oxide nanocomposite with high specific surface for use in solid phase microextraction of the antiepileptic drugs diazepam and oxazepam. Microchim Acta 185(6):312–320.

  2. 2.

    Rust KY, Baumgartner MR, Meggiolaro N, Kraemer T (2012) Detection and validated quantification of 21 benzodiazepines and 3 “z-drugs” in human hair by LC–MS/MS. Forensic Sci Int 215(1–3):64–72.

  3. 3.

    Laloup M, Fernandez MMR, Boeck De G, Wood M, Maes V, Samyn N (2005) Validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of 26 benzodiazepines and metabolites, zolpidem and zopiclone, in blood, urine, and hair. J Anal Toxicol 29(7):616–626.

  4. 4.

    Hackett J, Elian AA (2007) Extraction and analysis of clonazepam and 7-aminoclonazepam in whole blood using a dual internal standard methodology. Forensic Sci Int 166(2–3):209–217.

  5. 5.

    van der Merwe PJ, Steyn JM (1987) Thin-layer chromatographic method for determination of diazepam and its major metabolite, N-desmethyl diazepam, in human serum. J Chromatogr A 148(2):549–552.

  6. 6.

    Borrey D, Meyer E, Lambert W, Van Calenbergh S, Van Peteghem C, De Leenheer AP (2001) Sensitive gas chromatographic--mass spectrometric screening of acetylated benzodiazepines. J Chromatogr A 910(1):105–118.

  7. 7.

    Verplaetse R, Cuypers E, Tytgat J (2012) The evaluation of the applicability of a high pH mobile phase in ultrahigh performance liquid chromatography tandem mass spectrometry analysis of benzodiazepines and benzodiazepine-like hypnotics in urine and blood. J Chromatogr A 1249:147–154.

  8. 8.

    McClean S, OKane E, Hillis J, Smyth WF (1999) Determination of 1,4-benzodiazepines and their metabolites by capillary electrophoresis and high-performance liquid chromatography using ultraviolet and electrospray ionisation mass spectrometry. J Chromatogr A 838(1–2):273–291.

  9. 9.

    Bagheri H, Manshaei F, Rezvani O (2018) Three-dimensional nanofiber scaffolds are superior to two-dimensional mats in micro-oriented extraction of chlorobenzenes. Microchim Acta 185(7):322.

  10. 10.

    Mehrani Z, Ebrahimzadeh H, Aliakbar AR, Asgharinezhad AA (2018) A poly(4-nitroaniline)/poly(vinyl alcohol) electrospun nanofiber as an efficient nanosorbent for solid phase microextraction of diazinon and chlorpyrifos from water and juice samples. Microchim Acta 185(8):384.

  11. 11.

    Kumazawa T, Hasegawa C, Lee X-P (2007) Simultaneous determination of methamphetamine and amphetamine in human urine using pipette tip solid-phase extraction and gas chromatography–mass spectrometry. J Pharm Biomed Anal 44(2):602–607.

  12. 12.

    Amiri A, Ghaemi F (2017) Microextraction in packed syringe by using a three-dimensional carbon nanotube/carbon nanofiber–graphene nanostructure coupled to dispersive liquid-liquid microextraction for the determination of phthalate esters in water samples. Microchim Acta 184(10):3851–3858.

  13. 13.

    Rezayat MR, Jafari MT, Rahmanian F (2018) Thin film nanofibers containing ZnTiO3 nanoparticles for rapid evaporation of extraction solvent: application to the preconcentration of chlorpyrifos prior to its quantification by ion mobility spectrometry. Microchim Acta 186(1):35.

  14. 14.

    Tannu NS, Wu J, Rao VK, Gadgil HS, Pabst MJ, Gerling IC, Raghow R (2004) Paraffin-wax-coated plates as matrix-assisted laser desorption/ionization sample support for high-throughput identification of proteins by peptide mass fingerprinting. Anal Biochem 327(2):222–232.

  15. 15.

    Hsieh HC, Sheu C, Shi FK, Li DT (2007) Development of a titanium dioxide nanoparticle pipette-tip for the selective enrichment of phosphorylated peptides. J Chromatogr A 1165(1–2):128–135.

  16. 16.

    Bagheri H, Aghakhani A (2012) Polyaniline-nylon6 electrospun nanofibers for head spacead sorptive microextraction. Anal Chim Acta 713:63–69.

  17. 17.

    Stankusa JJ, Guan J, Fujimotoc K, Wagner WR (2006) Microintegrating smooth muscle cells into a biodegradable, elastomeric fiber matrix. Biomaterials 27(5):735–744.

  18. 18.

    Wang X, Hsiao BS (2016) Electrospun nanofiber membranes. Curr Opin Chem Eng 12:62–81.

  19. 19.

    Ren J, Musyoka NM, Annamalai P, Langmi HW, North BC, Mathe M (2015) Electrospun MOF nanofibers as hydrogen storage media. Int J Hydrog Energy 40(30):9382–9387.

  20. 20.

    Koo WT, Choi SJ, Kim S-J, Jang J-S, Tuller HL, Kim ID (2016) Heterogeneous sensitization of metal-organic framework driven metal@metal oxide complex catalysts on oxide nanofiber scaffold toward superior gas sensors. J Am Chem Soc 138(40):13431–13437.

  21. 21.

    Furukawa H, Cordova KE, O'Keeffe M, Yaghi OM (2013) The chemistry and applications of metal-organic frameworks. Science 341(6149):1230444–1230456.

  22. 22.

    Gu Z-Y, Chen Y-J, Jiang J-Q, Yan X-P (2011) Metal–organic frameworks for efficient enrichment of peptides with simultaneous exclusion of proteins from complex biological samples. Chem Commun 47(16):4787–4789.

  23. 23.

    Ge D, Lee HK (2011) Water stability of zeolite imidazolate framework 8 and application to porous membrane-protected micro-solid-phase extraction of polycyclic aromatic hydrocarbons from environmental water samples. J Chromatogr A 1218(47):8490–8495.

  24. 24.

    Férey G, Mellot-Draznieks C, Serre C, Millange F (2005) Crystallize frameworks with Giant pores: are there limits to the possible? Cheminform 36(29):217–225.

  25. 25.

    Asiabi M, Mehdinia A, Jabbaria A (2015) Preparation of water stable methyl-modified metal–organicframework-5/polyacrylonitrile composite nanofibers viaelectrospinning and their application for solid-phase extraction oftwo estrogenic drugs in urine samples. J Chromatogr A 1426:24–32.

  26. 26.

    Yang Z, Xu X, Liang X, Lei C, Wei Y, He P, Lv B, Ma H, Lei Z (2016) MIL-53(Fe)-graphene nanocomposites: efficient visible-light photocatalysts for the selective oxidation of alcohols. Appl Catal B 198:112–123.

  27. 27.

    Gu Z-Y, Yang C-X, Chang N, Yan X-P (2012) Metal–organic frameworks foranalytical chemistry: from sample collection to chromatographic separation. Acc Chem Res 45:734–745.

  28. 28.

    Gao Y, Lia S, Lia Y, Yao L, Zhanga H (2016) Accelerated photocatalytic degradation of organic pollutant over metal-organic framework MIL-53(Fe) under visible LED light mediated by persulfate. Appl Catal B Environ 202:165–174.

  29. 29.

    Liang R, Jing F, Shen L, Qin N, Wu L (2015) MIL-53(Fe) as a highly efficient bifunctional photocatalyst for the simultaneous reduction of Cr(VI) and oxidation of dyes. J Hazard Mater 287:364–372.

  30. 30.

    Bairros AV, Menck de Almeida R, Pantaleão L, Barcellosc T, Moura e Silva S, Yonamine M (2015) Determination of low levels of benzodiazepines and their metabolitesin urine by hollow-fiber liquid-phase microextraction (LPME) and gas chromatography–mass spectrometry (GC–MS). J Chromatogr B 975:24–33.

  31. 31.

    Goudarzi N, Farsimadan S, Chamjangali MA, Bagherian GA (2015) Optimization of modified dispersive liquid–liquid microextraction coupled with high-performance liquid chromatography for the simultaneous preconcentration and determination of nitrazepam and midazolam drugs: an experimental design. J Sep Sci 38(10):1673–1679.

  32. 32.

    Vardini MT, Mashayekhi HA, Saber-Tehrani M (2012) Dipersive liquid-liquid microextraction followed by high-performance liquid chromatography as an efficient and sensitive technique for the simultaneous determination of alprazolam, oxazepam, and diazepam in human urine samples. J Liq Chromatogr Relat Technol 35(7):988–999.

  33. 33.

    Fisichella M, Odoardi S, Strano-Rossi S (2015) High-throughput dispersive liquid/liquid microextraction (DLLME) method for the rapid determination of drugs of abuse, benzodiazepines and other psychotropic medications in blood samples by liquid chromatography- tandem mass spectrometry (LC-MS/MS) and application to forensic cases. Microchem J 123:33–41.

  34. 34.

    He H, Sun C, Wang X-R (2005) Solid-phase extraction of methadone enantiomers and benzodiazepines in biological fluids by two polymeric cartridges for liquid chromatographic analysis. J Chromatogr B 814(2):385–391.

  35. 35.

    Hegstad S, Oiestad EI, Johansen U, Christophersen AS (2006) Determination of benzodiazepines in human urine using solid-phase extraction and high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. J Anal Toxicol 30(1):31–37.

Download references

Author information

Correspondence to Homeira Ebrahimzadeh.

Ethics declarations

Conflict of interest

There are no conflicts to declare.

Additional information

Publisher’s note

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

Electronic supplementary material


(DOCX 717 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Amini, S., Ebrahimzadeh, H., Seidi, S. et al. Polyacrylonitrile/MIL-53(Fe) electrospun nanofiber for pipette-tip micro solid phase extraction of nitrazepam and oxazepam followed by HPLC analysis. Microchim Acta 187, 152 (2020).

Download citation


  • Composite nanosorbent
  • Miniaturization
  • Metal organic framework
  • Sample preparation
  • Microextraction
  • Benzodiazepines
  • Biological fluid
  • Waste water analysis