Automated System for ADME/T Assays

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Automated System for ADME/T Assays
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Within the drug discovery phase of pharmaceutical R&D several assays are widely used for lead optimisation. The applied techniques are summarised in the abbreviation ADME/T, which stands for Adsorption, Distribution, Metabolism, Elimination, and Toxicity. Physicochemical (or cell-free) assays comprise (LINK auf Sugen pdf) • Log D, Log P (for distribution) • Kinetic Solubility • PAMPA (Parallel artificial membrane permeability assay) • P450 activity (metabolism) These assays require a liquid handling workstation to handle aqueous phases as well as organic solvents. On-deck or off-deck shaking incubation is also often part of the assay. Compound distributions are typically analysed across the two sections of transwell plates (PAMPA) or across the organic and aqueous phases (Log assays) ...Read more

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Within the drug discovery phase of pharmaceutical R&D several assays are widely used for lead optimisation. The applied techniques are summarised in the abbreviation ADME/T, which stands for Adsorption, Distribution, Metabolism, Elimination, and Toxicity. Physicochemical (or cell-free) assays comprise (LINK auf Sugen pdf)

• Log D, Log P (for distribution)
• Kinetic Solubility
• PAMPA (Parallel artificial membrane permeability assay)
• P450 activity (metabolism)

These assays require a liquid handling workstation to handle aqueous phases as well as organic solvents. On-deck or off-deck shaking incubation is also often part of the assay. Compound distributions are typically analysed across the two sections of transwell plates (PAMPA) or across the organic and aqueous phases (Log assays) measured by UV spectroscopy or (LC)MS analysis. Thus, integration of incubators and readers or MS interfaces are typically part of ADME/T workstations.

Typical cell-based assays comprise:
• CaCo2 (permeability)
• Hepatocytes (metabolism)
• Microsomes (metabolism)

These assays usually require confinement of the robots in class 2 safety cabinets. After sample preparation, a shaking incubation takes place, followed by lysis and bulk (Hepatocytes, Microsomes) or compartmental (CaCo2) compound concentration determination by UV or (LC) MS. ADME/T assays are typically medium throughput assays, in the range of 50-100 compounds/day. HAMILTON offers various solutions for all the mentioned assays.

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Automated System for ADME/T Assays

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