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 Triple Quad 6500+ mass spectrometer for Quantitative Bioanalysis
- Exploris 120 High-Resolution Mass Spectrometers for Metabolite Characterisation
- Hamilton Star Liquid Handling Robot for HT-ADME Studies
- Microbeta Trilux Scintillation Counters for Radiochemical Profiling
- Quantulus GCT6220 Scintillation Counter for Radiochemical Detection
- Sorvall MTX150 Ultracentrifuge for Binding Studies
- LC-Jet Fraction Collector for Rapid Metabolite Profiling
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.