YBS Biographer Newsletter
Autumn/Winter 2012 Join our mailing list and download the latest and previous copies of our quarterly newsletter.
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In Vitro ADME

We provide a range of in vitro ADME assays from early discovery screens to definitive development studies.

With our state-of-the-art instrumentation, including:

  • AB SCIEX API 5000 mass spectrometers
  • AB SCIEX API 4000 mass spectrometers
  • Agilent 1290 high resolution LC systems
  • Hamilton MicroLab Star robots

We provide rapid generic automated screens or bespoke assays designed and validated to meet clients' needs. All our assays incorporate appropriate control compounds to monitor performance as well as tailored LC-MS methods with fit-for-purpose quality criteria.

Our range of assays include:

  • Metabolic stability in microsomes, hepatocytes, liver fractions, blood and plasma
  • Binding to plasma proteins, tissues and microsomes using either the Rapid Equilibrium Dialysis (RED) device or ultracentrifugation 
  • Blood:plasma partitioning
  • Chemical solution stability
  • Reaction phenotyping for P450s (3A4, 2D6, 2C9, 2C19, 1A2, 2B6 and 2C8) using multiple HLM batches, chemical inhibitors and recombinant enzymes
  • P450 inhibition (single point to full IC50) using probe substrates for 3A4, 2D6, 2C9, 2C19, 1A2, 2B6 and 2C8, including time-dependent inhibition
  • Reactive metabolites using conjugation with glutathione or alternative nucleophiles
Our in-house metabolite characterisation capability means that we can provide metabolism information in parallel with quantitative  in vitro data, notably impacting chemical design strategies by identifying sites of metabolic vulnerability to modulate high intrinsic clearance and elucidating reactive metabolic pathways to alleviate bioactivation.

As well as early discovery screening, we also conduct definitive plasma protein binding and blood:plasma partitioning studies for development compounds, using fully validated LC-MS/MS methods or radiochemical detection, as well as enzymology packages in support of regulatory submissions including inhibition and reaction phenotyping.

For further information on our in vitro ADME services and to discuss your specific requirements please contact us on +44 (0) 1904 686060 or email
info@yorkbio.com

 


 

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