A5028483864- Analytical Chemistry and Chromatography
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Analytical chemistry methods development
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Signaling Pathways in Disease
- Microfluidic and Capillary Electrophoresis Applications
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- French Urban and Social Studies
- Neuroscience and Neuropharmacology Research
- Analytical Methods in Pharmaceuticals
- Biochemical and Molecular Research
- Alcohol Consumption and Health Effects
- Antioxidant Activity and Oxidative Stress
- Tryptophan and brain disorders
- HIV/AIDS drug development and treatment
- Pesticide Residue Analysis and Safety
- Synthesis and Characterization of Heterocyclic Compounds
- Nitric Oxide and Endothelin Effects
- Colorectal Cancer Treatments and Studies
- Neurogenetic and Muscular Disorders Research
Roche (Switzerland)
2002-2022
École Polytechnique
2015
École nationale des ponts et chaussées
2015
The application of a new hybrid RF/DC quadrupole-linear ion trap mass spectrometer to support drug metabolism and pharmacokinetic studies is described. instrument based on quadrupole path capable conventional tandem spectrometry (MS/MS) as well several high-sensitivity MS scans using the final linear trap. Several pharmaceutical compounds, including trocade, remikiren tolcapone, were used evaluate capabilities system with positive negative turbo ionspray, either information-dependent data...
Antisense oligonucleotides linked by phosphorothioates are an important class of therapeutics under investigation in various pharmaceutical companies. may be coupled to high-affinity ligands (triantennary N-acetyl galactosamine = GalNAc) for hepatocyte-specific asialoglycoprotein receptors (ASGPR) enhance uptake hepatocytes and increase potency. Since disposition biotransformation GalNAc-conjugated is different from unconjugated oligonucleotides, appropriate analytical methods required...
Off-line solid phase extraction with C18 disk plates and turbulent flow chromatography were evaluated versus on-line using column-switching HPLC as sample preparation techniques for high-throughput analysis of pharmaceutical compounds their metabolites by LC-MS/MS. Turbulent was found to be very straightforward in its applicaton, but the LOQs more than fivefold higher compared off-line or other methods. Solid (SPE) on fast sufficient efficient minimize matrix effects therefore an apprach...
The in vivo biotransformation of a novel fusion protein tetranectin/apolipoprotein A1 (TN-ApoA1) was investigated by ligand-binding mass spectrometry (LB-MS) support enzyme-linked immunosorbent assays (ELISA). main focus on catabolites formed proteolysis the rabbit following intravenous administration lipidated TN-ApoA1. drug and its were isolated from plasma immunocapture with monoclonal antibody (mAb) binding to region captured released streptavidin-coated magnetic beads, separated...
A liquid chromatographic/mass spectrometric (LC/MS) assay was developed for the simultaneous determination of a pro-drug (Ro 48-3657), its active metabolite (platelet inhibitor, Ro 44-3888) and precursor 48-3656) in human, dog rat plasma, utilizing on-line column-switching solid-phase extraction (SPE) clean-up high-performance chromatography (HPLC) separation analytes, with detection by ionspray (pneumatically assisted electrospray) tandem mass spectrometry selected reaction monitoring (SRM)...
1. Tofogliflozin is a novel and selective SGLT2 inhibitor increasing glucosuria by inhibition of glucose re-absorption in the kidney for treatment type 2 diabetes mellitus.
1. The emerging technique of employing intravenous microdose administration an isotope tracer concomitantly with [14C]-labeled oral dose was used to characterize the disposition and absolute bioavailability a novel metabotropic glutamate 5 (mGlu5) receptor antagonist under clinical development for major depressive disorder (MDD). 2. Six healthy volunteers received single 1 mg [12C/14C]-basimglurant (2.22 MBq) concomitant i.v. 100 μg [13C6]-basimglurant. Concentrations [12C]-basimglurant...
A coupled liquid chromatography/tandem mass spectrometry assay was developed for simultaneous determination of Ro 48-6791 and its secondary amine metabolite in human plasma samples with a quantification limit both compounds 1 pg/mL using mL aliquot. The method exploits the enhanced sensitivity microbore (300 μm i.d.) reversed-phase capillary column to an ion spray probe combined tandem spectrometry. straightforward column-switching system utilized focus analytes onto trapping following...
Antisense oligonucleotides (ASOs) are chemically modified nucleic acids with therapeutic potential, some of which have been approved for marketing. We performed a study in rats to investigate mechanisms toxicity after administration 3 tool locked acid (LNA)-containing ASOs differing established safety profiles. Four male per group were dosed once, 3, or 6 times subcutaneously, 7 days between dosing, and sacrificed the last dose. These either unconjugated (naked) conjugated...
Abstract A novel approach to tritium-labeled antisense oligonucleotides (ASO) was established by conjugating N -succinimidyl propionate, as well maleimide-derivatives, the 3′-end of ASOs targeting metastasis-associated lung adenocarcinoma transcript 1 (Malat1) containing amino- or sulfhydryl-linkers. In vitro stability and Malat1 RNA reduction studies demonstrated that -ethylmaleimide (NEM) could be used a stable tag while maintaining desired target interaction. The corresponding radioactive...
Abstract As more and protein biotherapeutics enter the drug discovery pipelines, there is an increasing interest in tools for mechanistic metabolism investigations of biologics order to identify prioritize most promising candidates. Understanding or even predicting vivo clearance support translational pharmacokinetic modeling activities essential, however a lack effective validated vitro cellular tools. Although different mechanisms have be adressed context disposition, scope not comparable...
Abstract Vemurafenib is a BRAF kinase inhibitor indicated for the treatment of patients with V600 mutation–positive unresectable or metastatic melanoma and Erdheim‐Chester disease. This phase 1, open‐label, single‐arm study was designed to estimate absolute bioavailability oral vemurafenib at steady state characterize pharmacokinetics single intravenous microdose 14 C‐labeled in malignancies. Patients received 960 mg twice daily on days 1 through 28, infusion solution (3 mL, corresponding...
Dunkerque et son port ont longtemps eu une relation ambivalente. Ville de marche que se sont souvent disputée les Anglais, Français Flamands, a vu développement bridé par des enjeux militaires. Après sa quasi destruction en 1945, reconstruction Trente Glorieuses durablement consacré le destin industriel Dunkerque, un qui traduit urbanisation polders agricoles l’artificialisation la moitié du littoral département Nord. La crise économique années 1980 entraînera l’apparition gigantesques...
HPLC coupled to atmospheric pressure ionisation mass spectrometry has almost replaced assays with UV, fluorescence, or electrochemical detection, due its enhanced speed, sensitivity, and selectivity, especially when tandem-MS is used. To increase the speed sensitivity of drug further, high-speed HPLC, multi-component analysis, µHPLC are used on a routine basis. Sample preparation recognized as an important issue in bioanalytics. The use 96-well plate format automated liquid-handling systems,...