Cross-linked poly(ionic liquid)s were successfully used for the first time in the preparation of oligonucleotide biological samples. The adsorbents were prepared by co-polymerization of imidazolium-based ionic liquids and divinylbenzene. Consequently, the following three adsorbents were prepared and comprehenzively characterized: poly(3-butyl-1-vinylimidazolium bromide-co-divinylbenzene), poly(3-hexyl-1-vinylimidazolium bromide-co-divinylbenzene) and poly(2-(1-vinylimidazoliumyl)acetate-co-divinylbenzene). Oligonucleotides were adsorbed onto the surface of these materials at low pH values. Preliminary studies of the desorption of the analytes included testing the influence of different types of salts, as well as their concentrations and pH, and organic solvents on the recovery. This allowed for determining the adsorbent and the desorption conditions for further optimization with the use of central composition design. The chosen adsorbent was poly(2-(1-vinylimidazoliumyl)acetate-co-divinylbenzene), and the optimal desorption conditions (5 mM ammonium acetate (pH = 9.5)/methanol (50/50, v/v)) gave a recovery of 99.7 ± 0.3%. The dispersive micro-solid-phase extraction procedure was successfully applied for the extraction of oligonucleotides with various modifications and lengths. Finally, the developed method was used to extract 2'-O-methyl oligonucleotide and its two synthetic metabolites from enriched human plasma without any pre-purification, yielding recoveries over 80%.
Keywords: Antisense oligonucleotides; Dispersive micro-solid phase extraction; Serum samples; poly(ionic liquid)s.
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