Quintara Biosciences

Stability

Assay Matrices

Quintara provides a wide variety of metabolic stability assays using the following assay matrices:

  • Liver and intestinal microsomes (human and animal species)
  • Liver and intestinal S9 (human and animal species)
  • Liver cytosol (human and animal species)
  • Hepatocytes (human and animal species)
  • Plasma (human and animal species)
  • Blood (human and animal species)

Assay Results

  • Percent of remaining of parent compounds between +/- cofactor NADPH (microsomes or S9)
  • Percent of remaining of parent compounds between 0 minute and a fixed time (10, 30, or 60 minutes)
  • Intrinsic clearance determined by parent compound disappearance over six time points

CYP450 Inhibition

Enzymes/Substrates (All FDA Preferred)

  • CYP1A2/Phenacetin or Tacrine
  • CYP2B6/Efavirenz
  • CYP2C8/Taxol
  • CYP2C9/Tolbutamide
  • CYP2C19/S-mephenytoin
  • CYP2D6/Bufuralol
  • CYP3A4/Midazolam and Testosterone
  • Other CYP450 isoforms

CYP450 Inhibition Assay Formats

  • IC50 values generated by 7-point dose response curves
  • Percent of inhibition at fixed compound concentration

CYP450 MBI/TDI Assay Formats

  • IC50 shift after preincubation with and without cofactor NADPH using HLM
  • Inactivation kinact and KI determination using HLM or human hepatocytes
  • Irreversible and pseudo-irreversible inhibitor determination by potassium ferricyanide
  • Dialysis and ultrafiltration
  • Supernatant precipitation
  • Partition ratio determination

Detection Formats

  • LC/MS/MS detection with single substrate
  • LC/MS/MS detection with cocktail substrates
  • RapidFire/MS/MS detection with single substrate
  • RapidFire/MS/MS detection with cocktail substrates

Transporters

Assay Formats

  • P-gp substrate determination by MDR1-MDCK cells (High-throughput)
  • P-gp substrate determination by MDR1-MDCK and MDCK-II cells (FDA recommended method)
  • P-gp inhibitor determination by MDR1-MDCK and MDCK-II cells (FDA recommended method)

Bioanalysis

Assay and Sample Format

  • We utilize SCIEX API 4000 and API 5000 triple-quadrupole mass spectrometers for robust and sensitive quantitation. We can routinely determine compounds at pg level.
  • Shimadzu Prominence UFLC system provides low carryover, short runtime, and 96-well plate rack changer holding 12 plates for injection in refrigerated condition.
  • We provide qualitative analysis, such as screening for unknown chemicals or metabolites, using various modes of the mass spectrometers.
  • Caliper Sciclone ALH3000 robotic system provides versatile liquid handling and sample preparation capabilities for high data precision, great process speediness, and less human errors.
  • We utilize various sample cleanup strategies such as protein precipitation, liquid-liquid extraction, and solid phase extraction. Very small sample size is needed and the samples may contain multiple analytes and be in various matrices, including plasma, urine, cell culture, tissue samples.

Pharmacokinetics

  • In-life PK, TK available through our local partnership, which allows the shortest turnaround time and integrity of the studies.
  • Pharmacokinetics modeling provided using WinNonlin software.

Other Assays

Other Assays Available

  • CYP1A2, CYP2B6, and CYP3A4 induction in hepatocytes (functional assay and mRNA evaluations)
  • Plasma Protein Binding (human and animal species)
  • Reaction Phenotyping (parent disappearing)
  • Kinetic solubility (using DMSO stocks): fast and doesn't need a lot of material
  • Thermodynamic solubility (using solid compounds): gold standard
  • Passive diffusion determination by MDCK cells
  • Permeability by Caco-2 cells: gold standard
  • Label-free detection for biochemical or cell-based samples with RapidFire technology
  • Analytical chemistry: chemical or formulation analysis

Please contact us if you have any other ADME needs. We will be your partner in achieving your drug discovery goals.