Designing an "all-in-one" microextraction capsule device for the liquid chromatographic-fluorescence determination of doxorubicin and its metabolites in rat plasma.

In this study, an "all-in-one" microextraction device was designed and fabricated for the extraction of doxorubicin and its two metabolites from rat plasma prior to their determination by high performance liquid chromatography coupled to fluorescence detector. A sol-gel-based sorbent was synthesized in situ and incorporated within two conjoined porous polypropylene tubes together with a cylindrical magnetic bar in order to avoid the need of an external stirring bar. Among other sorbents investigated, the moderately polar sol-gel poly(tetrahydrofuran) was found to be advantageous due to its high affinity toward the target analytes. Systematic investigation of the critical parameters affecting the adsorption and the desorption step was carried out. Due to the "built-in" filtration mechanism of the porous microextraction capsules, the isolation of the analytes was performed directly in the plasma matrix without any previous sample pretreatment (i.e., protein precipitation, centrifugation, etc.). The proposed method was validated in terms of linearity, accuracy, precision, specificity, sensitivity, and stability according to the FDA guidelines. The limits of detection ranged between 1 - 2 ng mL while the lower limits of quantitation of the analytes were calculated as 10 ng mL. The accuracy (% relative error) was found within -9.7 - 15.3% under both intra- and inter-day conditions. The precision was better than 13.4% in all cases. ComplexGAPI index was employed to present the green attributes of the developed protocol from the preparation of the microextraction device to the final determination of the analytes. Finally, the applicability of the fabricated stand-alone extraction device was demonstrated in the analysis of the target analytes in rat plasma after intravenous administration of doxorubicin in order to assess its pharmacokinetic profile.