Notes

Glucagon-like peptide Only two analogues from the management of digestive tract failure: Any qualitative investigation of the opinions regarding sufferers in addition to their people throughout making decisions.
In T. cruzi, a causative agent of Chagas disease, phosphoenolpyruvate carboxykinase (TcPEPCK) is associated with carbohydrate catabolism. Tasquinimod Due to its importance in the metabolism of the parasite, it has become a promising target for the development of new drugs against Chagas disease. Aiming to investigate different approaches for ligands screening, TcPEPCK was immobilized on amine-terminated magnetic beads (TcPEPCK-MB) and kinetically characterized by liquid chromatography tandem mass spectrometry activity assay with a KMapp value of 10 ± 1 μM to oxaloacetate as substrate. Natural products library affords highly diverse molecular frameworks through their secondary metabolites, herein a ligand fishing TcPEPCK-MB assay is described for prospecting ligands in four ethanolic extracts of Brazilian Cerrado plants Qualea grandiflora (Vochysiaceae), Diospyros burchellii (Ebenaceae), Anadenanthera falcata (Fabaceae) and Byrsonima coccolobifolia (Malpighiaceae). The chemical characterization of eleven identified ligands was carried out by liquid chromatography tandem high-resolution mass spectrometry experiments. Senecic acid, syneilesinolide A, phytosphingosine and vanillic acid 4-glucopyranoside are herein reported for the first time for Q. grandiflora, D. burchellii, A. falcata, respectively. In addition, the specificity of the assay was observed since only catechin was fished out from the ethanolic extract of B. coccolobifolia leaves, despite the presence of epicatechin epimer.Bryophyllum pinnatum (Lam.) Oken (Crassulaceae) is widely used as leaf juice or extracts in traditional medicine all over tropical areas, especially in Brazil, to relieve inflammation-associated symptoms. Flavonol glycosides with unusual sugar moiety are among the major metabolites. Nevertheless, there are not enough quality control studies that can contribute to authentication of B. pinnatum and determination of their markers. As it is also used as medicinal plant in several countries, it is necessary to provide data related to safety, efficacy and quality. In this context, this work aims to isolate the major flavonoids from B. pinnatum hydroethanolic extract, to validate a method to quantify the content of chemical markers and to evaluate their xanthine oxidase inhibition and antioxidant activity. The extract was submitted to centrifugal partition chromatography (CPC). The solvents system CyHex-EtOAc-EtOH-H2O, 0.5935.5, v/v/v/v was selected by shake-flask method. Four flavonoids (quercetin 3-O-α-L-arabinopyμM) and 3 (124 μM) moderately inhibited XO, while compounds 1 and 3 displayed average radical scavenging activity. In conclusion, our results suggest the flavonoid 1 as a specific marker which may be used for quality control of B. pinnatum hydroethanolic leaves extract.Propofol is a widely used intravenous anesthetic for sedation during the surgery and worldwide propofol abuse has been frequently reported also. As an essential procedure for sample pretreatment, solid-phase extraction (SPE) is generally time-consuming and labor-intensive, which hindered the further improvement in the analysis of propofol from biological fluids. In this study, a rapid C18 pipette-tip based SPE method was developed to pretreat human plasma samples directly, bypassing the need for protein precipitation. The experiment conditions were optimized for the best extraction recovery (23.6 ± 4.1 %). After pretreatment, the plasma propofol was determined with liquid chromatography atmospheric-pressure chemical ionization-tandem mass spectrometry (LC-APCI-MS/MS) using propofol-d17 as the internal standard. The quantification method showed good linearity in the range of 0.005-5 μg mL-1 (r2 = 0.9992). The sensitivity, specificity, accuracy (90.0-113.3 %), precision (2.0-8.9 %), and stability (95.6-102.1 %) were satisfied for bioanalytical analysis. Finally, the concentrations of propofol in the plasma of a patient under anesthesia were determined with the proposed method and compared with the theoretical concentrations calculated with a population pharmacokinetics (popPK) model. In general, this work provided a rapid and straightforward method for the study of propofol in pharmacokinetics and forensic science.To explore the MS fragmentation pattern of synthetic cannabinoids by electrospray ionization mass spectrometry, twenty-seven synthetic cannabinoids were systematically investigated by liquid chromatography coupled to high-resolution quadrupole Orbitrap mass spectrometry(LC-Q-Orbitrap/MS)with positive mode of electrospray ionization. Based on tandem multistage MS and high resolution MS data, MS fragmentation pattern of synthetic cannabinoids was summarized. The cleavage of CC bonds next to the oxygen at the side chain on the C-3 position of synthetic cannabinoids was the characteristic fragmentation pathway of synthetic cannabinoids in the positive mode of electrospray ionization. When the synthetic cannabinoids with a 3-carbamoylpropyl-indole/indazole structure, NH3, CO, NH2CHO and CH2(CH3)2 were easy to lose to form different ions. While when the synthetic cannabinoids with a 3-carboxamide-indole/indazole structure, the side chain on the C-3 position was susceptible to γ-cleavage. In addition, this MS fragmentation pattern was applied to quickly screen whether electronic cigarette oil and tobacco from drug cases contain synthetic cannabinoids. This kind of compounds had strong fragmentation pattern, which provided new evidence for the rapid structure identification of synthetic cannabinoids.A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of dabrafenib (DAB), its main metabolite hydroxy-dabrafenib (OHD) and trametinib (TRA) in human plasma has been developed and validated. After addition of internal standard (dabrafenib-d9), extraction was achieved after protein precipitation with acetonitrile containing 1 % (v/v) formic acid. Chromatographic separation was performed on an Accucore® C18 (2.1 × 50 mm; 2.6 μm) column using a gradient elution of water acidified with 0.1 % (v/v) formic acid (A) and acetonitrile containing 0.1 % (v/v) formic acid (B) at a flow rate of 500 μL/min. The calibration ranged from 10 to 2000 ng/mL for DAB and OHD and from 5 to 50 ng/mL for TRA. This method was validated with satisfactory results including good precision (intra- and inter-assay coefficient of variation from 2.0 %-14.9 %) and good accuracy (inter- and intra-day bias between -1.2 % and 10.9 %), as well as long term stability in unprocessed plasma at -20 °C.
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