Non-regulated Bioanalysis

Comprehensive Bioanalytical Services for Non-Regulated Studies

We provide a rapid fit-for-purpose bioanalytical service for non-regulated in vitro and in vivo studies, undertaking quantitative LC-MS/MS analysis of drugs, metabolites and biomarkers in a range of matrices, including plasma, blood, urine, bile, tissue homogenates and in vitro samples.

Key Services:

• Comprehensive bioanalytical services for both regulated and non-regulated studies
• Rapid, fit-for-purpose quantitative LC-MS/MS analysis for in vivo studies
• Expertise in challenging peptide drug analyses (pg/mL LLOQ)
• LC-MS/MS quantitation of drugs, metabolites, and biomarkers across a range of species
• Discovery PK, PKPD, and exploratory toxicology assessments
• Expert troubleshooting skills to resolve bioanalytical issues
• Complex analysis including unusual matrices, conjugates, peptides, and multi-dimensional methods
• Tailored approach to methodology and reporting

Applications: Our services support early preclinical and clinical studies, enabling the rapid progression of drug programs by providing critical pharmacokinetic data. Non-regulated bioanalysis is typically performed in three species with 4-6 animal studies in the program, contracted as individual FFS projects over 6-12 months.

Instrumentation: We utilize a range of advanced technologies, including:

• LC-MS/MS systems (Waters™ Xevo TQ Absolute, SCIEX™ TQ 6500+)
• UPLC and HPLC systems (Waters™ Acquity UPLC, Agilent 1290)

In Vitro ADME

Tailored In Vitro ADME Assays for Drug Discovery and Development

We offer a comprehensive range of in vitro ADME assays, from early discovery screens to definitive development studies. Our services include rapid generic automated screens and bespoke assays designed and validated to meet clients' needs.

Key Services:

• Comprehensive in vitro ADME assays from early discovery to development
• Tailored assay design and validation to meet client needs
• Metabolic stability and liability assessments across multiple species
• Binding studies to plasma proteins, tissues, and microsomes (equilibrium dialysis/ultracentrifugation/ultrafiltration)
• Blood:plasma partitioning and reaction phenotyping
• Inhibition studies of P450s/UGTs
• Permeability and absorption studies using Caco-2 and MDCK cell lines
• Identification of reactive metabolites and evaluation of physicochemical properties

Applications: Our services help understand drug behavior and inform chemical design strategies by identifying metabolic vulnerabilities. We support regulatory submissions through comprehensive data generation and facilitate understanding of absorption, distribution, metabolism, and excretion (ADME) profiles for drug candidates.

Instrumentation: We utilize advanced technologies, including:

• AB SCIEX Triple Quad 6500+ for quantitative analysis
• Orbitrap and Q-Tof High-Resolution Mass Spectrometers
• Hamilton Star Liquid Handling Robot for HT-ADME studies

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