Synthesis and study of a molecularly imprinted polymer for specific solid-phase extraction of vinflunine and its metabolite from biological fluids.

A molecularly imprinted polymer (MIP) was synthesized in order to specifically extract vinflunine, an anticancer agent, and its metabolite (4-O-deacetylvinflunine) from bovine plasma and artificial urine by solid-phase extraction (SPE). Vinorelbine, a non-fluorinated analogue of vinflunine, was selected as a template for MIP synthesis. The selectivity of MIP versus the template (vinorelbine) and other alkaloids (catharanthine, vinblastine, vincristine, vinflunine and 4-O-deacetylvinflunine) was shown by a SPE protocol carried out with non-aqueous samples. A second protocol was developed for aqueous samples with two consecutive washing steps (AcOH–NH2OH buffer (pH 7, I=10 mM)–MeOH mixture 95:5 v/v and ACN–AcOH mixture 99:1 v/v) and an elution step (MeOH–AcOH mixture 90:10 v/v). Thus, MIP-SPE of bovine plasma brought high recoveries, 81 and 89% for vinflunine and its metabolite, respectively. This protocol was slightly modified for artificial urine samples in order to obtain a good MIP/NIP selectivity; furthermore, elution recoveries were 73 and 81% for vinflunine and its metabolite, respectively. Repeatability was assessed in both biological matrices and RSD (%) were inferior to 4%. The MIP also showed a suitable linearity (r2 superior to 0.99), between 0.25 and 10 μg/mL for plasma, and between 1 and 5 μg/mL for artificial urine.