Biotransformation
Our specialists in metabolite characterisation conduct bespoke in vitro experiments, MIST comparisons, ³H and ¹⁴C ADME studies, SAD/MAD studies, and enzymology investigations from early discovery through to clinical trials.
Comprehensive Biotransformation Services
We provide data and scientific insight to help address key biotransformation challenges, which may inform chemical design, compound selection, drug development strategies, and regulatory submissions. We identify and monitor metabolites throughout the development pipeline via metabolite profiling with LC-UV-HRMS and radiochemical detection in a range of in vitro and in vivo samples.
Key Services:
- Comprehensive metabolite characterisation from early discovery in vitro studies to late-stage radiolabelled studies
- In vitro incubations using microsomes, cytosol, S9 fractions, and hepatocytes across multiple species
- Metabolite profiling by LC-MS/UV/radiochemical detection
- Metabolite identification by LC-HRMS
- Analysis of in vitro and in vivo samples (plasma, urine, faeces, bile, tissue)
- Radiochemical detection using on-line (β-RAM; LAURA) or off-line (Scintiplate; Microbeta & Lumaplate; TopCount) techniques
- Application of chemical methods such as TiCl₃, methylation, H₂¹⁸O treatment, and Meisenheimer complexes
- Semi-quantitative MIST assessment using LC-MS/MS
- Cross-species comparison of steady-state exposure
- Metabolite generation and isolation from in vitro and in vivo samples by semi-preparative HPLC
- NMR analyses (1D: ¹H, ¹³C, ¹⁹F and 2D: COSY, NOESY, HMBC, HSQC)
- Expert chromatographic method development for complex matrices
- Analysis of novel modalities including oligonucleotides, peptides, ADCs, and other conjugates
Our advanced metabolite identification and profiling services are designed to support drug metabolism studies and inform drug development decisions
Applications: Our services assist with the characterisation of metabolic pathways to inform chemical design, identify active and reactive components, and support safety studies throughout drug discovery and development. We provide data for both early discovery and late-stage development, including:
- Early discovery studies to identify metabolic hot spots and inform chemical design
- Cross-species in vitro and in vivo studies to inform toxicology programmes
- Early development (SAD/MAD) studies for enzymology, active/reactive metabolites, and MIST assessments
- Regulatory submission packages, including radiolabelled studies in humans and toxicology species
Instrumentation: We utilise advanced technologies, including:
- Waters Vion IMS QTof, Thermo Q Exactive, and Exploris Orbitrap high-resolution mass spectrometers
- Waters Acquity and Agilent 1290 high-resolution LC systems
- Advanced NMR systems for in-depth structural analysis