In the current research experiment, a sensitive, precise and rapid bioanalytical approach involving the detection of fedratinib concentrations in rat plasma by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was optimized and established, and it was employed to describe the changes of fedratinib concentrations after oral treatment with various antifungal drugs (isavuconazole, posaconazole, fluconazole and itraconazole). An Acquity UPLC BEH reverse-phase C18 column (2.1 mm × 50 mm, 1.7 μm) was used for chromatographic separation of fedratinib and bosutinib (as internal standard (IS) in our study) under a linear gradient elution of the mobile phase, which was composed of solution A (acetonitrile) and solution B (water with 0.1% formic acid), along with 0.40 ml/min flow rate. The analyte and internal standard were measured with electrospray ion source in positive ion mode on a XEVO TQS triple quadrupole tandem mass spectrometer. The newly developed UPLC-MS/MS assay displayed enough linearity within the concentration range of 0.5–500 ng/ml for calibration curve. The intra- and inter-day of precision and accuracy were evaluated and validated to meet the requirements for the guidelines of bioanalytical assay. In addition, the findings of matrix effect, recovery, and stability were all within the acceptable limits. The new UPLC-MS/MS method was also successfully applied to characterize the pharmacokinetic changes of fedratinib in rats in the present of different antifungal drugs (such as isavuconazole, posaconazole, fluconazole and itraconazole). It turned out that fluconazole resulted in a prominent inhibitory effect on fedratinib metabolism in rats, followed by treatment with itraconazole and isavuconazole. Therefore, the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors may occur.
A novel molecularly imprinted optosensing material (MIOM) based on ionic liquid (IL)-stabilized CdSe/ZnS quantum dots (QDs) was prepared, for highly selective and sensitive recognition of the mycotoxin zearalenone (ZON). ZON is expensive and highly toxic, so the ZON analog cyclodo-decanyl-2,4dihydroxybenzoate (CDHB) was instead used as the template. MIOM was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and adsorption experiment.Under optimal conditions, the relative fluorescence intensity of MIOM decreased linearly with increasing ZON concentration, in the range of 0.003-3.12 mmol L À1 . MIOM had a detection limit of 0.002 mmol L À1 .MIOM was used to detect ZON in corn, rice and wheat flours, and at three concentration levels 50, 100 and 500 ng g À1 , ZON recoveries for these three cereals were 94.2-98.7%, 93.1-107.6% and 84.4-106.0%, respectively.
Photodynamic therapy (PDT) as a safe, non-invasive modality for cancer therapy, in which the low oxygen and high glutathione in the tumor microenvironment reduces therapeutic efficiency. In order to overcome these problems, we prepared a supramolecular photosensitive system of O2-Cu/ZIF-8@ZIF-8@WP6–MB (OCZWM), which was loaded with oxygen to increase the oxygen concentration in the tumor microenvironment, and the Cu2+ in the system reacted with glutathione (GSH) to reduce the GSH concentration to generate Cu+. It is worth noting that the generated Cu+ can produce the Fenton reaction, thus realizing the combination therapy of PDT and chemodynamic therapy (CDT) to achieve the purpose of significantly improving the anti-cancer efficiency.
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