Biotransformation, antipsychotics, BBB, BMVECs, cell-based metabolomics, LC-MS, multivariate data analysis Most studies of antipsychotic-therapies have highlighted the discrepancy between plasma and brain pharmacokinetics of antipsychotics, but how the drug changes through the blood brain barrier (BBB) has not been investigated. Cell-based metabolomics using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis were applied for screening of antipsychotic metabolites in the BBB. We applied this approach to analyze the antipsychotic biotransformation in brain microvascular endothelia cells (BMVECs), the main component of the BBB. From this study, five, four, three, and one metabolite of chlorpromazine, clozapine, haloperidol and risperidone, respectively, were locally metabolized on the BMVECs. These results confirm that there is a drug biotransformation process within the BBB and show that drug metabolite screening employed cellbased metabolomics using LC-MS, combined with multivariate analysis in the study of BMVECs exposed to antipsychotics can provide a way to screen drug metabolites in the BBB.
The physical aging of amorphous polymers induces changes in material properties, which are challenging to detect in situ in industrial settings. Here, we present a nondestructive nonlinear ultrasonic evaluation technique that enables localized measurements of the combined effects of temperature and time in amorphous polymers, without needing to remove materials. The proposed technique is demonstrated using commercial grade poly(vinyl chloride) samples and is supported by analysis of wave–material interactions. The results show that the physical aging of the polymer is described by the Arrhenius equation with an effective activation energy of 103 kJ/mol over the analyzed temperature range.
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