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Bioanalytical and ADME assays and services list

Q2 Solutions operates one of the world’s largest and most respected bioanalytical services laboratory networks. We represent a leading clinical trial laboratory services organization with bioanalytical, genomics, vaccines, flow cytometry, anatomic pathology, immunoassay, companion diagnostics and central laboratory services with secure, enterprise-wide biospecimen and consent management solutions. Recognizing that a clinical assay must be reliable over a period of years, Q2 Solutions benchmarks all projects using a rigorous bioanalytical method development strategy that includes a common set of SOPs, statistical analysis, and science writing support.

From in vitro ADME screening and discovery and development metabolite identification to DMPK services and regulatory validation, we can help you navigate your large-scale clinical study. Our integrated drug metabolism solutions include high-throughput screening assays, human clearance predictions, drug-drug interaction risk assessments and metabolite profiling to support clinical safety. In addition to the services listed below, we can also provide bundled services for discovery and regulatory-phase packages to enable decision-making in early discovery through IND and beyond.

Bioanalytical/Pharmacokinetics Services
Discovery Phase Bioanalysis by LC-MS/MS Details
Tiered bioanalysis service available Levels 0 – 3 (all non-regulated)
Bioanalytical with optional Pharmacokinetic Analysis: Plasma, Tissues Species selectable, non-compartmental analysis
Bioanalytical with optional Pharmacokinetic Analysis: Dried Blood Spot Species selectable, non-compartmental analysis

 

In Vitro ADME Services
High-Throughput Screening Assays Details
Solubility/Permeability Assays:  
    Solubility: Turbidimetric
 10 μM to 100 μM in buffer
    Permeability: MDCK
 MDCK (wild type), MDCK-II cell lines
    Permeability: PAMPA
 Pre-coated PAMPA plate system
Metabolic Stability Assays:  
    Metabolic Stability: Single Point
 Hepatocytes or microsomes; Species selectable
    Metabolic Stability: Intrinsic Clearance
 Hepatocytes or microsome; Species selectable
    Metabolic Stability: Plasma or S9
 Species selectable
Inhibition Assays (enzyme):  
    P450 Inhibition: Reversible Single Point
 Single concentration, P450 selectable (up to seven)
P450 Inhibition: Reversible IC50 Multiple concentrations, P450 selectable (up to seven)
    Time Dependent P450 Inhibition: Single Point
 Single concentration, CYP3A
    Time Dependent P450 Inhibition: Multiple Point
 CYP3A, CYP2B6, CYP2C8, CYP2C9, CYP2C19
        Time Dependent P450 Inhibition: IC50 Shift
 CYP3A or CYP3A4, 2D6 and 2C9 cocktail assays
Inhibition Assays (transporter):  
    Transporter Inhibition: Bile Salt Export Pump (BSEP) Inhibition
 Vesicles
Reaction Phenotyping Assays:  
    P450 Reaction Phenotyping: Substrate Depletion
 Microsomes with inhibitors for CYP2C9, CYP2D6, CYP3A
Other Assays:  
    Protein Binding: Plasma, Microsomes, Brain Homogenate, HSA, AAG
 Equilibrium dialysis HTDialysis or RED devise; Species selectable
    Blood to Plasma Ratio
 Species Selectable
Bundled Tier 1 Screening Assays:  
    Metabolic stability, permeability, CYP inhibition
 Human liver microsomes, MDCK, CYPs 2C9, 2D6, 3A in cocktail
Late Stage Discovery to Regulatory Phase Assays Details
Metabolic Stability Assays:  
    Metabolic Stability: Intrinsic Clearance
 Hepatocytes and microsomes; Species selectable (±ABT optional)
    Metabolic Stability: Glucuronidation (UGT) Clearance
 Microsomes (liver, intestine, kidney); Species selectable (±BSA)
    Metabolic Stability: Low Turnover Drugs
 Hepatocyte coculture systems (HµREL); Species selectable
Inhibition Assays (enzyme):  
    P450 Inhibition: Hepatocytes Suspended in Plasma
 CYP2C9, CYP2D6, CYP3A; combined reversible and TDI inhibition model
      P450 Inhibition: Reversible IC50
 Definitive IC50 for up to 7 P450s/8 assays
          P450 Inhibition: Reversible K
i		 Definitive Ki for selected P450s
        Time Dependent P450 Inhibition: I50 Shift
 IC50 shift following 30 min pre-incubation (part of reversible inhibition IC50 assay)
    Time Dependent P450 Inhibition: Kinetics
 CYPs 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A; kinact / KI and CLinact
    Time Dependent P450 Inhibition: Mechanism
 Metabolic intermediate (MI) complex formation, CYP3A4
      UGT Inhibition: Reversible IC50
 UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B7; Definitive IC50 using human liver microsomes
Induction Assays:  
    P450 Induction: mRNA discovery screen in human hepatocytes
 CYP1A2, CYP2B6, CYP3A4 message RNA assay following 24 hour treatment
    P450 Induction: mRNA in 3 human hepatocyte donors with Relative Induction Score
 CYP3A4, CYP2B6, CYP1A2, CYP2C8, CYP2C9, CYP2C19 mRNA, 48 or 72 hour treatment with basic DDI modeling (± CYP activity evaluation)
Reaction Phenotyping Assays:  
    Hepatocytes with pan-CYP inhibitor (ABT)
 Estimate CYP vs. non-CYP mediated fraction of metabolism
    P450 Reaction Phenotyping: Substrate Depletion
 Combination of rCYPs to predict HLM fm,CYP using RAF and/or chemical inhibitors
    P450 Reaction Phenotyping: Metabolite Formation
 Combination of rCYPs and/or chemical inhibitors
      Estimation of Fraction Metabolized by CYP3A4 and CYP3A5
    Aldehyde Oxidase (AO) Reaction Phenotyping: Human
 Combination of rCYPs and/or chemical inhibitors (ketoconazole and CYP3cide)
Human cytosol or hepatocytes ±Hydralazine (AO inhibitor)
Other Assays:  
    Protein Binding: Equilibrium Dialysis by HTDialysis Method
 Plasma, microsomes, HSA, AAG; Species selectable; human clinical plasma
    Blood to Plasma Ratio
 Human
Bundled IND-Enabling Assays:  
    In Vitro DDI: CYP inhibition, time-dependent inhibition (TDI) and induction
 HLMs and human hepatocytes; Assays meet regulatory guidelines for IND

 

Metabolite Profiling and Identification Discovery Services
Discovery to Regulatory Phase Assays Details (Waters Synapt G2-S and Thermo OrbiTrap and Q-Exactive HRMS)
Metabolite Profiling and Identification: Microsomes and Hepatocytes Species selectable; S9, cytosol, or hepatocyte coculture systems available
P450 Reaction Phenotyping: Metabolite Formation Microsomes with inhibitors for CYP1A2, CYP2C9, CYP2D6, CYP3A
Metabolite Profiling and Identification: In Vivo Services Plasma, urine, bile, feces, and/or tissue homogenate; Species selectable
Metabolite Profiling and Identification: Exploratory Profiling Exploratory assessment using unlabeled drug; Preclinical or clinical samples
Metabolite Profiling and Identification: Radioprofiling and MetID Preclinical or clinical samples; Typically plasma, urine, bile, and/or feces
Reactive Intermediate Screen: Glutathione or Cyanide Trapping Agent Microsomes; Species selectable
Reactive Intermediate Screen: Covalent Binding Radiolabel covalent binding in microsomes or hepatocytes, species selectable

 

>50 proprietary, large molecule assays performed in 2018

A full range of bioanalytical and ADME services

Q2 Solutions operates one of the world’s largest and most respected bioanalytical and ADME laboratory networks. From our global locations, we serve many of the largest pharmaceutical, specialty pharmaceutical and biotechnology companies in North America, South America, Europe and Asia. Our highly trained scientists utilize a range of leading-edge technology, automation and state-of-the-art techniques.

  • In Vitro ADME Assay development and metabolite identification services in support of rapid drug discovery ADME property optimization and regulatory filings
  • Bioanalytical liquid chromatography tandem mass spectrometry (LC/MS/MS) services for the quantitative determination of small molecule drugs and macromolecule therapeutics in support of pharmacokinetic (PK) studies
  • Immunoassay services for Enzyme-Linked ImmunoSorbant Assays (ELISA), mesoscale (MSD), electrochemiluminescence (ECL), and neutralizing antibody assays (NAB) in support of PK and immunogenicity studies
  • Biomarker services for LC/MS and ligand-binding assays for the quantitative determination of bioanalytical biomarkers

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