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Combination of magnetic dispersive micro solid-phase extraction and supramolecular solvent-based microextraction followed by high-performance liquid chromatography for determination of trace amounts of cholesterol-lowering drugs in complicated matrices


A novel, efficient, rapid, simple, sensitive, selective, and environmentally friendly method termed magnetic dispersive micro solid-phase extraction combined with supramolecular solvent-based microextraction (Mdμ-SPE–SSME) followed by high-performance liquid chromatography (HPLC) with UV detection is introduced for the simultaneous microextraction of cholesterol-lowering drugs in complicated matrices. In the first microextraction procedure, using layered double hydroxide (LDH)-coated Fe3O4 magnetic nanoparticles, an efficient sample cleanup is simply and rapidly provided without the need for time-consuming centrifugation and elution steps. In the first step, desorption of the target analytes is easily performed through dissolution of the LDH-coated magnetic nanoparticles containing the target analytes in an acidic solution. In the next step, an emulsification microextraction method based on a supramolecular solvent is used for excellent preconcentration, ultimately resulting in an appropriate determination of the target analytes in real samples. Under the optimal experimental conditions, the Mdμ-SPE–SSME–HPLC–UV detection procedure provides good linearity in the ranges of 1.0–1500 ng mL-1, 1.5–2000 ng mL-1, and 2.0–2000 ng mL-1 with coefficients of determination of 0.995 or less, low limits of detection (0.3, 0.5, and 0.5 ng mL-1), and good extraction repeatabilities (relative standard deviations below 7.8%, n = 5) in deionized water for rosuvastatin, atorvastatin, and gemfibrozil, respectively. Finally, the proposed method is successfully applied for the determination of the target analytes in complicated matrices.

Mdμ-SPE–SSME procedure

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  1. 1.

    Shah Y, Iqbal Z, Ahmad L, Khan A, Khan MI, Nazir S, et al. Simultaneous determination of rosuvastatin and atorvastatin in human serum using RP-HPLC/UV detection: method development, validation and optimization of various experimental parameters. J Chromatogr B. 2011;879:557–63.

    CAS  Article  Google Scholar 

  2. 2.

    Novakova L, Šat.nsk D, Solich P. HPLC methods for the determination of simvastatin and atorvastatin. Trends Anal Chem. 2008;27:352–67.

    CAS  Article  Google Scholar 

  3. 3.

    Ardila JA, Oliveira GG, Medeiros RA, Fatibello-Filho O. Determination of gemfibrozil in pharmaceutical and urine samples by square-wave adsorptive stripping voltammetry using a glassy carbon electrode modified with multi-walled carbon nanotubes within a dihexadecyl hydrogen phosphate film. J Electroanal Chem. 2013;690:32–7.

    CAS  Article  Google Scholar 

  4. 4.

    Arghavani-Beydokhti S, Asghari A, Bazregar M, Rajabi M. Application of a tandem airagitated liquid–liquid microextraction technique based on solidification of floating organic droplets as an efficient extraction method for determination of cholesterol-lowering drugs in complicated matrices. RSC Adv. 2016;6:93582–9.

    CAS  Article  Google Scholar 

  5. 5.

    Sarafraz-Yazdi A, Amiri A. Liquid-phase microextraction. Trends Anal Chem. 2010;29:1–14.

    CAS  Article  Google Scholar 

  6. 6.

    Pan J, Zhang C, Zhang Z, Li G. Review of online coupling of sample preparation techniques with liquid chromatography. Anal Chim Acta. 2014;815:1–15.

    CAS  Article  Google Scholar 

  7. 7.

    Ahmadi K, Abdollahzadeh Y, Asadollahzadeh M, Hemmati A, Tavakoli H, Torkaman R. Chemometric assisted ultrasound leaching-solid phase extraction followed by dispersive solidification liquid–liquid microextraction for determination of organophosphorus pesticides in soil samples. Talanta. 2015;137:167–73.

    CAS  Article  Google Scholar 

  8. 8.

    Arghavani-Beydokhti S, Rajabi M, Bazregar M, Asghari A. Centrifuge-free dispersive liquid–liquid microextraction based on the salting-out effect followed by high performance liquid chromatography for simple and sensitive determination of polycyclic aromatic hydrocarbons in water samples. Anal Methods. 2017;9:1732–40.

    CAS  Article  Google Scholar 

  9. 9.

    Rajabi M, Haji-Esfandiari S, Barfi B, Ghanbari H. Ultrasound-assisted temperaturecontrolled ionic-liquid dispersive liquid-phase microextraction method for simultaneous determination of anethole, estragole, and para-anisaldehyde in different plant extracts and human urine: a comparative study. Anal Bioanal Chem. 2014;406:4501–12.

    CAS  Article  Google Scholar 

  10. 10.

    Hemmati M, Asghari A, Bazregar M, Rajabi M. Rapid determination of some beta-blockers in complicated matrices by tandem dispersive liquid-liquid microextraction followed by high performance liquid chromatography. Anal Bioanal Chem. 2016;408:8163–76.

    CAS  Article  Google Scholar 

  11. 11.

    Peyrovi M, Hadjmohammadi M. Extraction optimization of Loratadine by supramolecular solvent-based microextraction and its determination using HPLC. J Chromatogr B. 2015;980:41–7.

    CAS  Article  Google Scholar 

  12. 12.

    Rezaei F, Yamini Y, Moradi M, Ebrahimpour B. Solid phase extraction as a cleanup step before microextraction of diclofenac and mefenamic acid using nanostructured solvent. Talanta. 2013;105:173–8.

    CAS  Article  Google Scholar 

  13. 13.

    Moral A, Caballo C, Sicilia MD, Rubio S. Highly efficient microextraction of chlorophenoxy acid herbicides in natural waters using a decanoic acid-based nanostructured solvent prior to their quantitation by liquid chromatography–mass spectrometry. Anal Chim Acta. 2012;709:59–65.

    CAS  Article  Google Scholar 

  14. 14.

    Qin H, Qiu X, Zhao J, Liu M, Yang Y. Supramolecular solvent-based vortex-mixed microextraction: determination of glucocorticoids in water samples. J Chromatogr A. 2013;1311:11–20.

    CAS  Article  Google Scholar 

  15. 15.

    Seidi S, Yamini Y, Rezazadeh M. Combination of electromembrane extraction with dispersive liquid–liquid microextraction followed by gas chromatographic analysis as a fast and sensitive technique for determination of tricyclic antidepressants. J Chromatogr B. 2013;913:138–46.

    Article  Google Scholar 

  16. 16.

    Farajzadeh MA, Djozan D, Nouri N, Bamorowat M, Shalamzari MS. Coupling stir bar sorptive extraction-dispersive liquid–liquid microextraction for preconcentration of triazole pesticides from aqueous samples followed by GC-FID and GC-MS determinations. J Sep Sci. 2010;33:1816–28.

    CAS  Article  Google Scholar 

  17. 17.

    Jowkarderis M, Raofie F. Optimization of supercritical fluid extraction combined with dispersive liquid–liquid microextraction as an efficient sample preparation method for determination of 4-nitrotoluene and 3-nitrotoluene in a complex matrix. Talanta. 2012;88:50–3.

    CAS  Article  Google Scholar 

  18. 18.

    Liu B, Yan H, Qiao F, Geng Y. Determination of clenbuterol in porcine tissues using solidphase extraction combined with ultrasound-assisted dispersive liquid–liquid microextraction and HPLC–UV detection. J Chromatogr B. 2011;879:90–4.

    CAS  Article  Google Scholar 

  19. 19.

    Ebrahimzadeh H, Abedi H, Yamini Y, Adlnasab L. Molecular-imprinted polymer extraction combined with dispersive liquid–liquid micro-extractionfor ultra-preconcentration of mononitrotoluene. J Sep Sci. 2010;33:3759–66.

    CAS  Article  Google Scholar 

  20. 20.

    Anastassiades M, Lehotay SJ, Stajnbaher D, Schenck FJ. Fast and easy multiresidue method employing acetonitrile extraction/partitioning and "dispersive solid-phase extraction" for the determination of pesticide residues in produce. J AOAC Int. 2003;86:412–31.

    CAS  Google Scholar 

  21. 21.

    Ros O, Vallejo A, Olivares M, Etxebarria N, Prieto A. Determination of endocrine disrupting compounds in fish liver, brain, and muscle using focused ultrasound solid–liquid extraction and dispersive solid phase extraction as clean-up strategy. Anal Bioanal Chem. 2016;408:5689–700.

    CAS  Article  Google Scholar 

  22. 22.

    Rajabi M, Arghavani-Beydokhti S, Barfi B, Asghari A. Dissolvable layered double hydroxide as an efficient nanosorbent for centrifugeless air-agitated dispersive solid-phase extraction of potentially toxic metal ions from bio-fluid samples. Anal Chim Acta. 2017;957:1–9.

    CAS  Article  Google Scholar 

  23. 23.

    Chieh Fu S, Hwa Tzing S, Chang Chen H, Chen Wang Y, Hsien DW. Dispersive solid phase extraction combined with gas chromatography–chemical ionization mass spectrometry for the determination of N-nitrosamines in swimming pool water samples. Anal Bioanal Chem. 2012;402:2209–16.

    Article  Google Scholar 

  24. 24.

    Abdolmohammad-Zadeh H, Kohansal S, Sadeghi G. Nickel–aluminum layered double hydroxide as a nanosorbent for selective solid-phase extraction and spectrofluorometric determination of salicylic acid in pharmaceutical and biological samples. Talanta. 2011;84:368–73.

    CAS  Article  Google Scholar 

  25. 25.

    Coronado E, Mart.-Gastaldo C, Navarro-Moratalla E, Ribera A. Intercalation of [M(Ox)3] 3−(M= Cr, Rh) complexes into Ni II Fe III-LDH. Appl Clay Sci. 2010;48:228–34.

    CAS  Article  Google Scholar 

  26. 26.

    Mallakpour S, Dinari M. Hybrids of Mg–Al-layered double hydroxide and multiwalled carbon nanotube as a reinforcing filler in the l-phenylalanine-based polymer nanocomposites. J Therm Anal Calorim. 2015;119:1905–12.

    CAS  Article  Google Scholar 

  27. 27.

    Abdolmohammad-Zadeh H, Jouyban A, Amini R, Sadeghi G. Nickel-aluminum layered double hydroxide as a nano-sorbent for the solid phase extraction of selenium, and its determination by continuous flow HG-AAS. Microchim Acta. 2013;180:619–26.

    CAS  Article  Google Scholar 

  28. 28.

    Xia SJ, Ni ZM, Xu Q, Hu BX, Hu J. Layered double hydroxides as supports for intercalation and sustained release of antihypertensive drugs. J Solid State Chem. 2008;181:2610–9.

    CAS  Article  Google Scholar 

  29. 29.

    Sansuk S, Nanan S, Srijaranai S. New eco-friendly extraction of anionic analytes based on formation of layered double hydroxides. Green Chem. 2015;17:3837–43.

    CAS  Article  Google Scholar 

  30. 30.

    Saraji M, Ghani M. Dissolvable layered double hydroxide coated magnetic nanoparticles for extraction followed by high performance liquid chromatography for the determination of phenolic acids in fruit juices. J Chromatogr A. 2014;1366:24–30.

    CAS  Article  Google Scholar 

  31. 31.

    Tang S, Lee HK. Application of dissolvable layered double hydroxides as sorbent in dispersive solid-phase extraction and extraction by co-precipitation for the determination of aromatic acid anions. Anal Chem. 2013;85:7426–33.

    CAS  Article  Google Scholar 

  32. 32.

    Sui M, Zhou Y, Sheng L, Duan B. Adsorption of norfloxacin in aqueous solution by Mg–Al layered double hydroxides with variable metal composition and interlayer anions. Chem Eng J. 2012;210:451–60.

    CAS  Article  Google Scholar 

  33. 33.

    Zhao X, Liu S, Wang P, Tang Z, Niu H, Cai Y, et al. Surfactant-modified flowerlike layered double hydroxide-coated magnetic nanoparticles for preconcentration of phthalate esters from environmental water samples. J Chromatogr A. 2015;1414:22–30.

    CAS  Article  Google Scholar 

  34. 34.

    Yan Z, Yuan J, Zhu G, Zou Y, Chen C, Yang S, et al. A new strategy based on cholesterolfunctionalized iron oxide magnetic nanoparticles for determination of polycyclic aromatic hydrocarbons by high-performance liquid chromatography with cholesterol column. Anal Chim Acta. 2013;780:28–35.

    CAS  Article  Google Scholar 

  35. 35.

    Alonso EV, del Mar Guerrero M, Cueto PC, Bentez JB, Pavn JMC, de Torres AG. Development of an on-line solid phase extraction method based on new functionalized magnetic nanoparticles. Use in the determination of mercury in biological and sea-water samples. Talanta. 2016;153:228–39.

    Article  Google Scholar 

  36. 36.

    Can K, Ozmen M, Ersoz M. Immobilization of albumin on aminosilane modified superparamagnetic magnetite nanoparticles and its characterization. Colloids Surf B: Biointerfaces. 2009;71:154–9.

    CAS  Article  Google Scholar 

  37. 37.

    Wang J, Zhou J, Li Z, Song Y, Liu Q, Jiang Z, et al. Magnetic, luminescent Eu-Doped Mg–Al layered double hydroxide and its intercalation for ibuprofen. Chem Eur J. 2010;16:14404–11.

    CAS  Article  Google Scholar 

  38. 38.

    Farahani H, Norouzi P, Beheshti A, Sobhi HR, Dinarvand R, Ganjali MR. Quantitation of atorvastatin in human plasma using directly suspended acceptor droplet in liquid–liquid–liquid microextraction and high-performance liquid chromatography-ultraviolet detection. Talanta. 2009;80:1001–6.

    CAS  Article  Google Scholar 

  39. 39.

    Kang X, Wang F, Xie Z, Li H. A high performance liquid chromatography method for simultaneous determination of rosiglitazone and gemfibrozil in human plasma. J Chromatogr B. 2009;877:645–8.

    CAS  Article  Google Scholar 

  40. 40.

    Naeemullah TM, Kazi TG. Simple and green switchable dispersive liquid-liquid microextraction of cadmium in water and food samples. RSC Adv. 2016;6:28767–73.

    CAS  Article  Google Scholar 

  41. 41.

    Narapusetti A, Bethanabhatla SS, Sockalingam A, Repaka N, Saritha V. Simultaneous determination of rosuvastatin and amlodipine in human plasma using tandem mass spectrometry: application to disposition kinetics. J Adv Res. 2015;6:931–40.

    CAS  Article  Google Scholar 

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The authors gratefully acknowledge the financial support of Semnan University.

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Correspondence to Maryam Rajabi.

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The authors declare that they have no conflict of interest.

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All drug-free human urine and plasma samples used in this study were obtained from individual participants with their informed consent in accordance with institutional principles and standards. These studies were approved by Semnan University Research Council and were performed in accordance with ethical standards.

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Arghavani-Beydokhti, S., Rajabi, M. & Asghari, A. Combination of magnetic dispersive micro solid-phase extraction and supramolecular solvent-based microextraction followed by high-performance liquid chromatography for determination of trace amounts of cholesterol-lowering drugs in complicated matrices. Anal Bioanal Chem 409, 4395–4407 (2017).

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  • Magnetic dispersive micro solid-phase extraction
  • Supramolecular solvent-based microextraction
  • Layered double hydroxide-coated magnetic nanoparticles
  • Complicated matrices