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. 2021 Apr 1;22(7):3665.
doi: 10.3390/ijms22073665.

Magnetic Core-Shell Molecularly Imprinted Nano-Conjugates for Extraction of Antazoline and Hydroxyantazoline from Human Plasma-Material Characterization, Theoretical Analysis and Pharmacokinetics

Joanna Giebułtowicz  1 , Natalia Korytowska  1 , Monika Sobiech  2 , Sebastian Polak  3 , Barbara Wiśniowska  3 , Roman Piotrowski  4 , Piotr Kułakowski  4 , Piotr Luliński  2
Affiliations

Magnetic Core-Shell Molecularly Imprinted Nano-Conjugates for Extraction of Antazoline and Hydroxyantazoline from Human Plasma-Material Characterization, Theoretical Analysis and Pharmacokinetics

Joanna Giebułtowicz et al. Int J Mol Sci. .

Abstract

The aim of this study was to develop magnetic molecularly imprinted nano-conjugate sorbent for effective dispersive solid phase extraction of antazoline (ANT) and its metabolite, hydroxyantazoline (ANT-OH) in analytical method employing liquid chromatography coupled with mass spectrometry method. The core-shell material was characterized in terms of adsorption properties, morphology and structure. The heterogeneous population of adsorption sites towards ANT-OH was characterized by two Kd and two Bmax values: Kd (1) = 0.319 µg L-1 and Bmax (1) = 0.240 μg g-1, and Kd (2) = 34.6 µg L-1 and Bmax (2) = 5.82 μg g-1. The elemental composition of magnetic sorbent was as follows: 17.55, 37.33, 9.14, 34.94 wt% for Si, C, Fe and O, respectively. The extraction protocol was optimized, and the obtained results were explained using theoretical analysis. Finally, the analytical method was validated prior to application to pharmacokinetic study in which the ANT was administrated intravenously to three healthy volunteers. The results prove that the novel sorbent could be useful in extraction of ANT and ANT-OH from human plasma and that the analytical strategy could be a versatile tool to explain a potential and pharmacological activity of ANT and ANT-OH.

Keywords: antazoline; atrial fibrillation; biomedical applications; core–shell nanostructures; dispersive solid phase extraction; hydroxyantazoline; magnetic molecularly imprinted polymers; mass spectrometry; particle characterization.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
Distribution of atomic partial charges (ESP) in the molecules of ANT and ANT-O–. Molecules colored according to the partial charge values—negative values are shown as red and positive values as blue.
Figure A2
Figure A2
Results of optimization process of antazoline (ANT) and hydroxyantazoline (ANT-OH) extraction. Contact time of the analytes with the sorbent (a), type of washing solution (b) as well as time and type of elution solvent (c) were tested.
Figure A2
Figure A2
Results of optimization process of antazoline (ANT) and hydroxyantazoline (ANT-OH) extraction. Contact time of the analytes with the sorbent (a), type of washing solution (b) as well as time and type of elution solvent (c) were tested.
Figure 1
Figure 1
Freundlich isotherms for ANT (a) and ANT-OH (b) on mag-MIP and mag-NIP.
Figure 2
Figure 2
Scatchard plot for ANT-OH on mag-MIP and mag-NIP.
Figure 3
Figure 3
Kinetics data on mag-MIP and mag-NIP for ANT (a) and ANT-OH (b).
Figure 4
Figure 4
Views of ANT-O– (a) and ANT (b) at the end of the adsorption process in the MIP model cavity (monomers—green color); classical hydrogen bonds—green dashed lines; non-classical hydrogen bonds—red dashed lines; hydrophobic interactions—light violet dashed lines.
Figure 5
Figure 5
Micrographs of Fe3O4 (a), Fe3O4@SiO2-MPS (c) and mag-MIP (e) and EDS spectra of Fe3O4 (b), Fe3O4@SiO2-MPS (d) and mag-MIP (f).
Figure 5
Figure 5
Micrographs of Fe3O4 (a), Fe3O4@SiO2-MPS (c) and mag-MIP (e) and EDS spectra of Fe3O4 (b), Fe3O4@SiO2-MPS (d) and mag-MIP (f).
Figure 6
Figure 6
Extracted chromatogram of ANT (a) and ANT-OH (b) in blank plasma and lower limit of quantitation (LLOQ).
Figure 7
Figure 7
Pharmacokinetic profile of (a) antazoline (ANT) and its metabolite (b) hydroxyantazoline (ANT-OH) after intravenous administration of 100 mg antazoline mesylate to three volunteers.
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References

    1. Kojro G., Wroczyński P. Cloud Point Extraction in the Determination of Drugs in Biological Matrices. J. Chromatogr. Sci. 2019;58:151–162. doi: 10.1093/chromsci/bmz064. - DOI - PubMed
    1. BelBruno J.J. Molecularly Imprinted Polymers. Chem. Rev. 2019;119:94–119. doi: 10.1021/acs.chemrev.8b00171. - DOI - PubMed
    1. Crapnell R.D., Dempsey-Hibbert N.C., Peeters M., Tridente A., Banks C.E. Molecularly imprinted polymer based electrochemical biosensors: Overcoming the challenges of detecting vital biomarkers and speeding up diagnosis. Talanta Open. 2020;2:100018. doi: 10.1016/j.talo.2020.100018. - DOI
    1. Sobiech M., Bujak P., Luliński P., Pron A. Semiconductor nanocrystal–polymer hybrid nanomaterials and their application in molecular imprinting. Nanoscale. 2019;11:12030–12074. doi: 10.1039/C9NR02585E. - DOI - PubMed
    1. Wackerlig J., Lieberzeit P.A. Molecularly imprinted polymer nanoparticles in chemical sensing—Synthesis, characterisation and application. Sens. Actuators B Chem. 2015;207:144–157. doi: 10.1016/j.snb.2014.09.094. - DOI

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