"Off/On" Fluorescent Probe based on Aggregation-Induced Quenching of ZnO-Quantum dots for Determination of Ara-C: Pharmacokinetic Applications, Adsorption Kinetics & Green Profile Assessment.

Herein, a turn "Off/On" fluorescence probe based on ZnO quantum dots (ZnO-QDs) has been proposed and successfully utilized for the determination of Ara-C (cytarabine) using ceric ions (Ce) as quencher and ethylenediamine (ED) as a linker. The probe is based initially on the quenching effect of Ce ions on the strong native fluorescence of ZnO-QDs forming the Turn Off system (Ce@ZnO-QDs) that believed to occur due to the aggregation-induced quenching (AIQ) mechanism. The second step is the addition of Ara-C in the presence of ethylenediamine (ED) that encourages the formation of Ara-C/ED/Ce as well as the release of the free ZnO-QDs, leading to the recovery of the fluorescence intensity. The developed sensing platform shows a linear response towards Ara-C over the range of 10 to 1000 ng mL giving a limit of detection (LOD) and limit of quantitation (LOQ) of 1.22 ng mL and 3.70 ng mL, respectively. A dispersive magnetic solid phase micro-extraction (dMSPE) method was developed and optimized for the extraction of Ara-C in spiked human plasma using thiol-modified magnetite nanoparticles (S-MNPs). The proposed platform exhibits good sensitivity toward Ara-C in the presence of different interfering substances. Excellent recoveries are obtained after spiking different concentrations of Ara-C into rabbit plasma samples. The validated experimental parameters have been successfully applied to monitor the pharmacokinetic profile of Ara-C in rabbit plasma. A detailed adsorption kinetics study has been carried out to provide a deep insight into the adsorption behavior of Ara-C on the thiol-doped-magnetite nanoparticles. The greenness assessment of the proposed method was achieved and compared with other reported methods using two tools of greenness; the green analytical procedure index (GAPI) and the analytical greenness calculator AGREE.