Journal of the Iranian Chemical Society

, Volume 13, Issue 2, pp 289–298 | Cite as

Determination of widely used non-steroidal anti-inflammatory drugs in biological fluids using simultaneous derivatization and air-assisted liquid–liquid microextraction followed by gas chromatography–flame ionization detection

  • Mir Ali FarajzadehEmail author
  • Hassan Nasrollahpour
  • Mohammad Reza Afshar Mogaddam
  • Leila Khoshmaram
Original Paper


A sensitive and reliable method for the extraction, preconcentration, and determination of non-steroidal acidic anti-inflammatory drugs (ibuprofen, naproxen, and diclofenac) from biological samples has been developed using simultaneous derivatization and air-assisted liquid–liquid microextraction followed by gas chromatography–flame ionization detection. In this method, a mixture of an extraction solvent (chloroform) and a derivatizing agent (butyl chloroformate) is added into a glass test tube containing an aqueous sample of the analytes and picoline (catalyst). The mixture is dispersed by repeatedly aspirating and dispensing via a syringe. By this action, derivatization and extraction of the selected analytes is performed simultaneously. Under the optimal conditions, enrichment factors and extraction recoveries were obtained in the ranges 364–412 and 72–82 %, respectively. The linear ranges were broad with correlation coefficients higher than 0.995. Limits of detection were obtained in the ranges 0.06–3.30 and 0.24–13 ng mL−1 in urine and plasma samples, respectively. Limits of quantification were 0.21–9.2 ng mL−1 in urine and 0.84–37 ng mL−1 for plasma sample. Relative standard deviations were lower than 5.2 % for six repeated determinations at a concentration of 25 ng mL−1 of each analyte. Finally, the developed method was successfully applied to determine the selected analytes in urine and plasma samples.


Air-assisted liquid–liquid microextraction Non-steroidal anti-inflammatory drugs Gas chromatography Derivatization Biological fluids 



Air-assisted liquid–liquid microextraction


Dispersive liquid–liquid microextraction


Hollow fiber-liquid phase microextraction


High performance liquid chromatography


Gas chromatography


Flame ionization detector


Liquid–liquid extraction


Non-steroidal anti-inflammatory drug


Single drop microextraction


Solid phase extraction


Solid phase microextraction



Authors are grateful to Research Council of the University of Tabriz for financial support and scientific encouragement.


  1. 1.
    C.A. Bernsten, R.H. Freyberg, Ann. Intern. Med. 54, 938 (1961)CrossRefGoogle Scholar
  2. 2.
    G.B. Porro, F. Pace, I. Caruso, Aliment. Pharmacol. Ther. 1, 540 (1987)CrossRefGoogle Scholar
  3. 3.
    M.A.I. Espinoza, A.D.J.P. Guillen, O.H.A. Martinez, Br. J. Oral Maxillofac. Surg. 52, 775 (2014)CrossRefGoogle Scholar
  4. 4.
    S.J. Kim, A.J. Flach, L.M. Jampol, Surv. Ophthalmol. 55, 108 (2010)CrossRefGoogle Scholar
  5. 5.
    M. Petrović, M.D. Hernando, M.S. Díaz-Cruz, D. Barceló, J. Chromatogr. A 1067, 1 (2005)CrossRefGoogle Scholar
  6. 6.
    R. Lucena, M. Cruz-Vera, S. Cardenas, M. Valcarcel, Bioanalysis 1, 135 (2009)CrossRefGoogle Scholar
  7. 7.
    M.A. Jeannot, F.F. Cantwell, Anal. Chem. 68, 2236 (1996)CrossRefGoogle Scholar
  8. 8.
    H. Liu, P.K. Dasgupta, Anal. Chem. 68, 1817 (1996)CrossRefGoogle Scholar
  9. 9.
    M. Rezaee, Y. Assadi, M.R. Millani, E. Aghaee, F. Ahmadi, S. Berijani, J. Chromatogr. A 1116, 1 (2006)CrossRefGoogle Scholar
  10. 10.
    G. Khayatian, S.S. Hosseini, S. Hassanpoor, J. Iran. Chem. Soc. 10(6), 1167 (2013)CrossRefGoogle Scholar
  11. 11.
    O. Sha, J. Chen, L. Chen, S. Li, J. Iran. Chem. Soc. (2015). doi: 10.1007/s13738-015-0605-0 Google Scholar
  12. 12.
    M.A. Farajzadeh, M.R. Afshar Mogaddam, Anal. Chim. Acta 728, 31 (2012)CrossRefGoogle Scholar
  13. 13.
    I. Rodriguez, J. Carpinteiro, J.B. Quintana, A.M. Carro, R.A. Lorenzo, R. Cela, J. Chromatogr. A 1024, 1 (2004)CrossRefGoogle Scholar
  14. 14.
    M.R. Payana, M.A. Bello-Lopez, R. Fernandez-Torres, M.C. Mochona, J.L.G. Ariza, Talanta 82, 854 (2010)CrossRefGoogle Scholar
  15. 15.
    A. Sarafraz-Yazdi, A. Amiri, G. Rounaghi, H. Eshtiagh-Hosseini, J. Chromatogr. B 908, 67 (2012)CrossRefGoogle Scholar
  16. 16.
    A. Saleh, E. Larsson, Y. Yamini, J.Å. Jonsson, J. Chromatogr. A 1218, 1331 (2011)CrossRefGoogle Scholar
  17. 17.
    M. Cruz-Vera, R. Lucena, S. Cardenas, M. Valcarcel, J. Chromatogr. A 1202, 1 (2008)CrossRefGoogle Scholar
  18. 18.
    M. Dawod, M.C. Breadmore, R.M. Guijt, P.R. Haddad, J. Chromatogr. A 1216, 3380 (2009)CrossRefGoogle Scholar
  19. 19.
    H.H. Maurer, F.X. Tauvel, T. Kraemer, J. Anal. Toxicol. 25, 237 (2001)CrossRefGoogle Scholar
  20. 20.
    Z. Es’haghi, Anal. Chim. Acta 641, 83 (2009)CrossRefGoogle Scholar
  21. 21.
    A.M. Ferreira, M.E. Laespada, J.L. Pavón, B.M. Cordero, J. Chromatogr. A 1296, 70 (2013)CrossRefGoogle Scholar
  22. 22.
    C.H. Lee, Y. Shin, M.W. Nam, K.M. Jeong, J. Lee, Talanta 129, 552 (2014)CrossRefGoogle Scholar
  23. 23.
    M.K.R. Mudiam, R. Jain, M. Varshney, R. Ch, A. Chauhan, S.K. Goyal, H.A. Khan, R.C. Murthy, J. Chromatogr. B 925, 63 (2009)CrossRefGoogle Scholar
  24. 24.
    Y. Fan, Y.Q. Feng, S.L. Da, Z.H. Wang, Talanta 65, 111 (2005)Google Scholar
  25. 25.
    M.J. Gomez, A. Aguera, M. Mezcua, J. Hurtado, F. Mochol, A.R. Fernandez-Alba, Talanta 73, 314 (2007)CrossRefGoogle Scholar
  26. 26.
    L. Xu, M. Jiang, G. Li, Anal. Chim. Acta 666, 45 (2010)CrossRefGoogle Scholar

Copyright information

© Iranian Chemical Society 2015

Authors and Affiliations

  • Mir Ali Farajzadeh
    • 1
    Email author
  • Hassan Nasrollahpour
    • 1
  • Mohammad Reza Afshar Mogaddam
    • 1
  • Leila Khoshmaram
    • 2
  1. 1.Department of Analytical Chemistry, Faculty of ChemistryUniversity of TabrizTabrizIran
  2. 2.Department of Chemistry, Faculty of SciencesAzarbaijan Shahid Madani UniversityTabrizIran

Personalised recommendations