Recent advances in protein mass spectrometry (MS) have enabled determinations of hydrogen deuterium exchange (HDX) in large macromolecular complexes. HDX-MS became a valuable tool to follow protein folding, assembly and aggregation. The methodology has a wide range of applications in biotechnology ranging from quality control for over-expressed proteins and their complexes to screening of potential ligands and inhibitors.
View Article and Find Full Text PDFIn the present study, the metabolic profile of amlodipine, a well-known calcium channel blocker, was investigated employing liquid chromatography-mass spectrometric (LC/MS) techniques. Two different types of mass spectrometers - a triple-quadrupole (QqQ) and a quadrupole time-of-flight (Q-TOF) mass spectrometer - were utilized to acquire structural information on amlodipine metabolites. The metabolites were produced by incubation of amlodipine with primary cultures of rat hepatocytes.
View Article and Find Full Text PDFA high proportion of drugs are chiral compounds used as racemic mixtures in a clinical practice. Very often only one of two enantiomers exhibits a desired pharmacological effect. Amlodipine, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine, is a chiral calcium channel blocker, currently used as a racemate in clinical practice.
View Article and Find Full Text PDFA set of 48 derivatives of the tricyclic sesquiterpenol alcohol isolongifolol was synthesized. The set comprised homochiral and diastereomeric alcohols, amines, chlorohydrins, as well as carboxylic acids, phosphonic acids, and their corresponding esters. The absolute configuration of the epimeric compounds was assigned by 2D NMR experiments [gradient heteronuclear single quantum correlation (gHSQC) and gradient nuclear Overhauser enhancement spectroscopy (gNOESY)] in agreement with crystallographic data.
View Article and Find Full Text PDFThe purpose of this study was to test the applicability of n-in-one (cocktail) incubations in the determination of intrinsic clearance (Cl(int)) as the slope of the linear portion of the Michaelis-Menten curve (velocity V vs. substrate concentration [S]) where substrate concentrations were low. A rapid, sensitive, and selective liquid chromatography tandem mass spectrometry (LC/MS/MS) method was developed for the analysis of samples produced by single-substrate and n-in-one (seven substrates: entacapone, 17beta-estriol, umbelliferone, 4-methylumbelliferone, tolcapone, hydroxyquinoline, and paracetamol) incubations conducted in 96-well plates with different recombinant UDP-glucuronosyltransferases (UGTs).
View Article and Find Full Text PDFSibutramine is an anti-obesity drug sold as a racemic mixture under the trademark Meridia or Reductil. With the aim of evaluating the stereoselectivity in phase I of sibutramine biotransformation, the formation of the main metabolites from R -sibutramine, S -sibutramine and rac-sibutramine was studied in rat microsomes and primary cultures of hepatocytes. A novel analytical method for the determination of sibutramine and its phase I metabolites in culture medium and microsomal incubates using isocratic reversed-phase liquid chromatography with UV detection was developed.
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