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Research Article

Advancing the use of molecularly imprinted polymers in bioanalysis: the selective extraction of cotinine in human urine

    Haley A Mulder

    Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA

    ,
    Thomas I Cecil

    Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284, USA

    ,
    Cory Fines

    Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA

    ,
    Adam C Pearcy

    Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA

    &
    Matthew S Halquist

    *Author for correspondence: Tel.: +1 804 827 2078;

    E-mail Address: halquistms@vcu.edu

    Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA

    Published Online:https://doi.org/10.4155/bio-2023-0019

    Aim: To characterize a molecularly imprinted polymer via precipitation polymerization for the extraction of cotinine in urine. Methods: The polymer was created via precipitation polymerization. Physical characteristics of the polymer were assessed via scanning electron microscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis. The polymer adsorption capacity was assessed and an solid-phase extraction method from urine by LC–MS/MS was developed. Results: The polymer had small, spherical morphology and little thermal decomposition. The extraction method yielded cotinine recoveries of 77–103% in urine. The molecularly imprinted polymer adsorption capacity for cotinine was 448.2 ± 2.1 μg/mg. Common interferants did not affect cotinine's extraction. Conclusion: The resulting polymer was determined to be specific for cotinine and can be used for the detection of cotinine in urine for clinical samples.

    Papers of special note have been highlighted as: • of interest

    References

    • 1. Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol. Rev. 18(2), 188–204 (1996).
    • 2. Benowitz NL, Hukkanen J, Jacob P. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb. Exp. Pharmacol. 192, 29–60 (2009).
    • 3. Inukai T, Kaji S, Kataoka H. Analysis of nicotine and cotinine in hair by on-line in-tube solid-phase microextraction coupled with liquid chromatography–tandem mass spectrometry as biomarkers of exposure to tobacco smoke. J. Pharm. Biomed. Anal. 156, 272–277 (2018).
    • 4. Haufroid V, Lison D. Urinary cotinine as a tobacco-smoke exposure index: a minireview. Int. Arch. Occup. Environ. Health 71, 162–168 (1998).
    • 5. López-Rabuñal Á, Lendoiro E, González-Colmenero E et al. Assessment of tobacco exposure during pregnancy by meconium analysis and maternal interview. J. Anal. Toxicol. 44(8), 797–802 (2020).
    • 6. Marques H, Cruz-Vicente P, Rosado T et al. Recent developments in the determination of biomarkers of tobacco smoke exposure in biological specimens: a review. Int. J. Environ. Res. Public Health 18(4), 1–23 (2021).
    • 7. Pérez-Ortuño R, Martínez-Sánchez JM, Fernández E, Pascual JA. High-throughput wide dynamic range procedure for the simultaneous quantification of nicotine and cotinine in multiple biological matrices using hydrophilic interaction liquid chromatography–tandem mass spectrometry. Anal. Bioanal. Chem. 407(28), 8463–8473 (2015).
    • 8. Chadwick CA, Keevil B. Measurement of cotinine in urine by liquid chromatography tandem mass spectrometry. Ann. Clin. Biochem. 44, 455–462 (2007).
    • 9. Vasapollo G, Del Sole R, Mergola L et al. Molecularly imprinted polymers: present and future prospective. Int. J. Mol. Sci. 12(9), 5908–5945 (2011).
    • 10. Turiel E, Esteban AM. Molecularly imprinted polymers. In: Solid-Phase Extraction. Elsevier, 215–233 (2020).
    • 11. Boyd B, Lundberg D, Kronauer S et al. Tobacco-specific nitrosamines: efficient extraction of toxic compounds from complex matrices using molecularly imprinted polymers. (2007).
    • 12. Yang J, Hu Y, Cai J-B et al. A new molecularly imprinted polymer for selective extraction of cotinine from urine samples by solid-phase extraction. Anal. Bioanal. Chem. 384, 761–768 (2006).
    • 13. Larpant N, Suwanwong Y, Boonpangrak S et al. Exploring matrix effects on binding properties and characterization of cotinine molecularly imprinted polymer on paper-based scaffold. Polymers 11(3), 570 (2019). • Adsorption capacity of bulk polymerization polymer that was used for the extraction of cotinine – results from this study were compared with the adsorption capacity experiments conducted.
    • 14. Sorribes-Soriano A, Esteve-Turrillas FA, Armenta S, Amorós P et al. Amphetamine-type stimulants analysis in oral fluid based on molecularly imprinting extraction. Anal. Chim. Acta 1052, 73–83 (2019).
    • 15. Bouvarel T, Delaunay N, Pichon V. Selective extraction of cocaine from biological samples with a miniaturized monolithic molecularly imprinted polymer and on-line analysis in nano-liquid chromatography. Anal. Chim. Acta 1096, 89–99 (2020).
    • 16. Huang XH, Song JJ, Li H et al. Selective removal of nicotine from the main stream smoke by using a surface-imprinted polymer monolith as adsorbent. J. Hazard. Mater. 365, 53–63 (2019).
    • 17. Lu C, Li H, Xu M et al. Preparation of nicotine-imprinted monolith by in-situ surface imprinting onto internal hole surface of macroporous silica for selective enrichment and separation of nicotine in environmental water sample. Sep. Sci. Technol. 50, 2124–2133 (2015).
    • 18. Tan Y, Yin J, Liang C et al. A study of a new TSM bio-mimetic sensor using a molecularly imprinted polymer coating and its application for the determination of nicotine in human serum and urine. Bioelectrochemistry 53(2), 141–148 (2001).
    • 19. Zander SA, Findlay P, Renner T et al. Analysis of nicotine and its oxidation products in nicotine chewing gum by a molecularly imprinted solid-phase extraction. Anal. Chem. 70, 3304–3314 (1998).
    • 20. Yang J, Hu Y, Cai J-B et al. Selective hair analysis of nicotine by molecular imprinted solid-phase extraction: an application for evaluating tobacco smoke exposure. Food Chem. Toxicol. 45(6), 896–903 (2007). • Method for bulk polymerization to analyze cotinine in urine.
    • 21. Poole CF. Core concepts and milestones in the development of solid-phase extraction. In: Solid-Phase Extraction. Poole C (Ed.). Elsevier, 1–36 (2020).
    • 22. He C, Long Y, Pan J et al. Application of molecularly imprinted polymers to solid-phase extraction of analytes from real samples. J. Biochem. Biophys. Methods 70, 133–150 (2007).
    • 23. Zheng C, Huang YP, Liu ZS. Recent developments and applications of molecularly imprinted monolithic column for HPLC and CEC. J. Sep. Sci. 34, 1988–2002 (2011).
    • 24. Beltran A, Borrull F, Marcé RM et al. Molecularly-imprinted polymers: useful sorbents for selective extractions. TrAC 29(11), 1363–1375 (2010).
    • 25. Sambe H, Hoshina K, Moaddel R et al. Uniformly-sized, molecularly imprinted polymers for nicotine by precipitation polymerization. J. Chromatogr. A 1134(1–2), 88–94 (2006). • The landmark paper from which the precipitation method was adapted. Authors were the first to demonstrate that cotinine could bind to the polymer that was created.
    • 26. Beltran A, Marcé RM, Cormack PAG et al. Synthesis by precipitation polymerisation of molecularly imprinted polymer microspheres for the selective extraction of carbamazepine and oxcarbazepine from human urine. J. Chromatogr. A 1216(12), 2248–2253 (2009).
    • 27. Ho K-C, Yeh W-M, Tung T-S et al. Amperometric detection of morphine based on poly(3,4-ethylenedioxythiophene) immobilized molecularly imprinted polymer particles prepared by precipitation polymerization. Anal. Chim. Acta 542(1), 90–96 (2005).
    • 28. Mulder HA, Pearcy AC, Halquist MS. Characterization of molecularly imprinted polymers for the extraction of tobacco alkaloids and their metabolites in human urine. Biomed. Chromatogr. 36(6), e5361 (2022). • Previous paper from authors that characterized an SPE method for cotinine under similar conditions with a commercial polymer. The same commercial polymer was later assessed for thermogravimetric analysis in this study and compared with the polymer developed in-house.
    • 29. Hu T, Chen R, Wang Q et al. Recent advances and applications of molecularly imprinted polymers in solid-phase extraction for real sample analysis. J. Sep. Sci. 44(1), 274–309 (2021).
    • 30. Andersson LI, Paprica A, Arvidsson T. A highly selective solid phase extraction sorbent for pre-concentration of sameridine made by molecular imprinting. Chromatographia 46, 57–62 (1997).
    • 31. Andersson LI. Efficient sample pre-concentration of bupivacaine from human plasma by solid-phase extraction on molecularly imprinted polymers. Analyst 125, 1515–1517 (2000).
    • 32. Theodoridis G, Kantifes A, Manesiotis P et al. Preparation of a molecularly imprinted polymer for the solid-phase extraction of scopolamine with hyoscyamine as a dummy template molecule. J. Chromatogr. A 987, 103–109 (2003).
    • 33. Chapuis-Hugon F, Cruz-Vera M, Savane R et al. Selective sample pretreatment by molecularly imprinted polymer for the determination of LSD in biological fluids. J. Sep. Sci. 32(19), 3301–3309 (2009).
    • 34. Cela-Pérez MC, Bates F, Jiménez-Morigosa C et al. Water-compatible imprinted pills for sensitive determination of cannabinoids in urine and oral fluid. J. Chromatogr. A 1429, 53–64 (2016).
    • 35. Xia Y, McGuffey JE, Bhattacharyya S et al. Analysis of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanol in urine by extraction on a molecularly imprinted polymer column and liquid chromatography/atmospheric pressure ionization tandem mass spectrometry. Anal. Chem. 77(23), 7639–7645 (2005).
    • 36. Shah KA, Peoples MC, Halquist MS et al. Microfluidic direct injection method for analysis of urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) using molecularly imprinted polymers coupled on-line with LC–MS/MS. J. Pharm. Biomed. Anal. 54(2), 368–378 (2011).
    • 37. Chang X, Jiang N, Zheng H et al. Solid-phase extraction of iron(III) with an ion-imprinted functionalized silica gel sorbent prepared by a surface imprinting technique. Talanta 71(1), 38–43 (2007).
    • 38. Li X, Yu P, Feng Y et al. Specific adsorption and highly sensitive detection of methyl red in wastewater using an iron paste electrode modified with a molecularly imprinted polymer. Electrochem. Commun. 132, 107144 (2021).
    • 39. van Overmeire IPI, de Smedt T, Dendale P et al. Nicotine dependence and urinary nicotine, cotinine and hydroxycotinine levels in daily smokers. Nicotine Tob. Res. 18(9), 1813–1819 (2016).
    • 40. Benowitz NL, Jacob P. Trans-3′-hydroxycotinine: disposition kinetics, effects and plasma levels during cigarette smoking. Br. J. Clin. Pharmacol. 51, 53–59 (2001).