Biotransformation

Comprehensive Biotransformation Services

We provide both data and knowledge to clarify key biotransformation challenges, impacting chemical design, compound selection, drug development strategies, and regulatory submissions. Our experts in metabolite characterization cover bespoke in vitro experiments, MIST comparisons, 3H and 14C ADME studies, SAD/MAD studies, and enzymology investigations from early discovery through to clinical trials.

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:

• Full metabolite characterization from early discovery in vitro studies to late development radiolabeled 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, feces, bile, tissue)
• Radiochemical detection using on-line (β-RAM; LAURA) or off-line (Scintiplate; Microbeta & Lumaplate; TopCount) approaches
• Use of chemical techniques 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 unusual modalities including oligonucleotides, peptides, ADCs, and other conjugates

Applications: Our services aid in the characterization of metabolic pathways to inform chemical design, identify active and reactive components, and underwrite safety studies throughout drug discovery and development. We provide data for 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 programs
• Early development (SAD/MAD) studies for enzymology, active/reactive metabolites, and MIST assessments
• Definitive regulatory packages including radiolabeled studies in humans and toxicology species

Instrumentation: We utilize 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