A5084125112- Analytical Chemistry and Chromatography
- Pharmacogenetics and Drug Metabolism
- Mass Spectrometry Techniques and Applications
- Drug Transport and Resistance Mechanisms
- Receptor Mechanisms and Signaling
- Metabolomics and Mass Spectrometry Studies
- Analytical Methods in Pharmaceuticals
- Computational Drug Discovery Methods
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
- Microfluidic and Capillary Electrophoresis Applications
- Pharmacological Effects and Toxicity Studies
- Eicosanoids and Hypertension Pharmacology
- Genomics, phytochemicals, and oxidative stress
- Tryptophan and brain disorders
- Glutathione Transferases and Polymorphisms
- Pharmacological Receptor Mechanisms and Effects
- Diet and metabolism studies
- Analytical chemistry methods development
- Advanced biosensing and bioanalysis techniques
- HIV/AIDS drug development and treatment
- Synthesis and Biological Evaluation
- Nuclear Receptors and Signaling
- Bioactive Compounds and Antitumor Agents
- Drug-Induced Hepatotoxicity and Protection
Regulus Therapeutics (United States)
2023
Takeda (United States)
2018-2022
Novartis (United States)
2010-2016
Biogen (United States)
2016
Novartis (Switzerland)
2012-2015
Pfizer (United States)
2000-2012
To identify the cytochrome P450 (CYP) isoform(s) responsible for formation of primary metabolite ziprasidone (ziprasidone sulphoxide), to determine kinetics its and predict possible drug interactions by investigating CYP isoform inhibition in an vitro study.In metabolism [14C]-ziprasidone was studied using human liver microsomes. The metabolites were identified mass spectrometry. determined (10-200 microM) over 5 min, Km Vmax estimated from Lineweaver-Burk plots. IC50 values specific probe...
Electrospray ionization (ESI) and collisionally induced dissociation (CID) mass spectra were obtained for five tetracyclines the corresponding compounds in which labile hydrogens replaced by deuterium either gas phase or liquid exchange. The number of hydrogens, x, could easily be determined from a comparison ESI with N2 ND3 as nebulizer gas. CID [M + H]+ - H]- ions exchanged analogs, [M(Dx) D]+ D]- , produced using Sciex API-III(plus) Finnigan LCQ ion trap spectrometer. Compositions product...
The effects of various mobile-phase additives, solution pH, pKa, and analyte concentration on electrospray ionization mass spectra a series purine pyrimidine nucleoside antiviral agents were studied in both positive negative ion models. use 1% acetic acid resulted good HPLC separation the greatest sensitivity for [M + H]+ ions. In mode, 50 mM ammonium hydroxide gave - H]- sensitivities as ions significantly larger than agents. Vidarabine monophosphate agents, however, showed comparable or...
The effects of mobile-phase additives and analyte concentration on electrospray ionization mass spectra a series tetracyclines were investigated in both positive negative ion modes. Only [M + H](+) - H](-) ions observed. greatest sensitivity as was obtained with 1% acetic acid the using 50 mM ammonium hydroxide. Sensitivities mode greater than those mode. showed no systematic variation pH; however, did increase increasing pH. A larger linear range observed for ions. Both Na](+) 0.5 sodium...
Ziprasidone (Geodone), a novel atypical antipsychotic agent, is recently approved for the treatment of schizophrenia. It undergoes extensive metabolism in preclinical species and humans after oral administration, only very small amount administered dose excreted as unchanged drug. In vitro studies using human liver microsomes have shown that oxidative ziprasidone mediated primarily by CYP3A4. However, coadministration with ketoconazole, CYP3A4 inhibitor, showed modest increase its exposure....
In humans, approximately two-thirds of the metabolic clearance ziprasidone proceeds through reduction N-S bond benzisothiazole moiety, which is followed by methylation resulting thiophenol to major metabolite S-methyldihydroziprasidone. The objective this study was gain an understanding underlying mechanism route. Incubation in human liver cytosol yielded product dihydroziprasidone. Heating prior incubation prevented reaction, and reaction saturable (K(M) = 3.9 µM; V(max) 0.24 nmol/min/mg...
ESI and CID mass spectra were obtained for four pyrimidine nucleoside antiviral agents the corresponding compounds in which labile hydrogens replaced by deuterium using gas-phase exchange. The number of hydrogens, x, was determined from a comparison with N(2) ND(3) as nebulizer gas. [M + H](+) - H](-) ions exchanged analogs, [M(D(x)) D](+) D](-), produced SCIEX API-III(plus) spectrometer. Protonated dissociate through rearrangement decompositions base-protonated cleavage glycosidic bonds to...
RGLS4326 is a short oligonucleotide inhibitor of microRNA-17 (miR-17) that preferentially distributes to the kidney and displaces miR-17 from translationally active polysomes. Here, we present pharmacokinetics absorption, distribution, metabolism, excretion properties mice monkeys. was absorbed rapidly after subcutaneous administration, distributed extensively liver, with preferential distribution kidney, cleared plasma by tissue uptake renal excretion. Plasma exposure increased in...
Electrospray ionization (ESI) and collision-induced dissociation (CID) mass spectra were obtained for two purine nucleoside antiviral agents (acycloguanosine vidarabine) one nucleotide (vidarabine monophosphate) the corresponding compounds in which labile hydrogens replaced by deuterium gas-phase exchange. The number of hydrogens, x, was determined from a comparison ESI with N 2 ND 3 as nebulizer gas. CID [M + H] – − ions exchanged analogs, [M(D x ) D] , produced using Sciex API-III plus...
The role of propionitrile in the production [M+H]+ under atmospheric pressure photoionization (APPI) was investigated. In dopant-assisted APPI using acetone and anisole, protonated anisole radical cations were most prominent ions observed. dopant-free or direct acetonitrile, however, a major ion acetonitrile detected identified as propionitrile, high accuracy mass measurement collision induced dissociation studies. Vaporizing ca. 10(-5) M althiazide bendroflumethazide produced their...
A method is developed for the prediction of mass spectral ion counts drug-like molecules using in silico calculated chemometric data. Various data, including polar and molecular surface areas, aqueous solvation free energies, gas-phase proton affinities were computed, a statistically significant relationship between measured combination affinity total area was identified. In particular, through multilinear regression on predicted we find that log10(MS counts) = -4.824 + c 1•PA 2•SA, where PA...
Hepatic metabolism of low-clearance compound TAK-041 was studied in two different vitro model systems using rat, dog, monkey, and human suspended cryopreserved hepatocytes HepatoPac micropatterned coculture primary hepatocytes. The aim this work to investigate the most appropriate system assess biotransformation TAK-041, determine any notable species difference rate extent its metabolic pathways, establish correlation with vivo metabolism. exhibited very low turnover hepatocyte suspensions...
The metabolism, pharmacokinetics, and excretion of a potent selective 5-hydroxytryptamine<sub>1B</sub> receptor antagonist elzasonan have been studied in six healthy male human subjects after oral administration single 10-mg dose [<sup>14</sup>C]elzasonan. Total recovery the administered was 79% with approximately 58 21% radioactive excreted feces urine, respectively. average <i>t</i><sub>1/2</sub> for 31.5 h. Elzasonan extensively metabolized, excreta plasma were analyzed using mass...
In vitro metabolite identification and GSH trapping studies in human liver microsomes were conducted to understand the bioactivation potential of compound <b>1</b> [2-(6-(4-(4-(2,4-difluorobenzyl)phthalazin-1-yl)piperazin-1-yl)pyridin-3-yl)propan-2-ol], an inhibitor Hedgehog pathway. The results revealed formation a unique, stable quinone methide (M1) via <i>ipso</i> substitution fluorine atom subsequent adduct (M2). stability this arises from extensive resonance-stabilized conjugation...
The metabolism, pharmacokinetics, and excretion of a potent selective substance P receptor antagonist, CP-122,721 [(+)-(2<i>S</i>,3<i>S</i>)-3-(2-methoxy-5-trifluoromethoxybenzylamino)-2-phenylpiperidine], have been studied in six healthy male human subjects [four extensive metabolizers (EMs) two poor (PMs) CYP2D6) following oral administration single 30-mg dose [<sup>14</sup>C]CP-122,721. Approximately 84% the administered radioactivity was recovered from urine feces over period 312 h. 80%...