In this study, an online electrochemistry coupling high-performance liquid chromatography-mass spectrometry (EC-HPLC-MS) technology has been developed for simulating metabolic reactions and rapid analysis of metabolites of flavone, quercetin, and rutin, which are not only widely present compounds with pharmacological activity in nature, but also have structural similarity and variability. The simulated metabolic processes of the substrates (phase I and phase II metabolism) were implemented on the surface of glassy carbon electrode (GCE) by using different electrochemical methods. After online chromatographic separation, the products were transmitted to a mass spectrometer for detection, in order to speculate relevant reaction pathways and structural information of the reaction product. The main metabolites, including methylation, hydroxylation, hydrolysis, and conjugation reaction products, had been successfully identified through the designed in situ hyphenated technique. Furthermore, compared with metabolites produced by in vitro incubation of rat liver microsomes, it was found that the products of electrochemical simulated metabolism were more abundant with diverse metabolic pathways. The results indicated that the proposed method exhibited advantages in the sample pretreatment process and detection cycle without compromising the reliability and accuracy of the results. Graphical
As emerging alternatives of legacy perfluoroalkyl substances, perfluorophosphinates (PFPiAs) and perfluorophosphonates (PFPAs) are widely applied in industrial and agricultural fields and are supposed to be large partitioned to soil and highly persistent. It is of particular interest to understand their transfer from roots to shoots and transformation in plants, such as wheat. The results of hydroponic experiments indicated that C6/C6 PFPiA, C8/C8 PFPiA, perfluorooctanophosphonic acid (PFOPA), and perfluorohexaphosphonic acid (PFHxPA) were quickly adsorbed on the epidermis of wheat root (Triticum aestivum L.), which was driven by their hydrophobicity. A small fraction of the accumulated PFPiAs and PFPAs in the wheat root was subjected to absorption via an active process dependent on H+-ATPase. PFHxPA, which has the smallest molecular weight and medium hydrophilicity (log Kow < 4), displayed the strongest absorption efficiency via the water and anion channels and had the highest translocation potential from roots to shoots in wheat. C6/C6 and C8/C8 PFPiAs experienced phase I metabolism in wheat, although at a low rate, to form more persistent PFHxPA and PFOPA, respectively, as well as 1H-perfluorohexane (1H-PFHx) and 1H-perfluorooctane (1H-PFO), which were regulated by cytochrome P450 in wheat root. As a result, exposure to PFPiAs in roots ultimately caused the accumulation of more persistent PFPAs in the above-ground parts of plants, raising concerns on their potential risks on human health.
Yan Lou,Wenqi Qiu,Zhe Wu,Qian Wang,Yunqing Qiu,Su Zeng
We previously showed that BZG is a novel multitarget kinase inhibitor, which inhibited hepatocellular carcinoma in vivo and in vitro . In the present study, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) to characterize BZG and its metabolites generated in vivo . The probable metabolic mechanism was further confirmed by analysis of Phase I and Phase II metabolism in liver microsomes and with recombinant enzymes. In addition, the binding affinities of BZG metabolites to vascular endothelial growth factor receptor 2 (VEGFR2) were predicted using electronic high throughput screening (eHiTS). The results showed that BZG underwent phase I and phase II metabolism. We detected 11 BZG metabolites and identified hydroxylation, glucuronation, acetylation, sulfonation and degradation as the major metabolic processes in vivo and in vitro . Five of the eleven metabolites showed highly favorable eHiTS energy scores that were lower than sorafenib. Knowledge of the in vivo metabolic pathways of BZG and its binding affinities to VEGFR2 will be beneficial for further clinical development of BZG.
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