Preliminary BCS Solubility Classification – Shake-Flask
This non-GLP assay is used to determine a preliminary BCS solubility classification by measuring the quasi-equilibrium solubility of a test compound in aqueous USP buffer systems at two pH values between 1.0 and 7.4
Required from Customer
- A study design—the customer must specify the values of several assay variables listed in the Options section
- Minimum 50 mg of test compound in powder form
- Highest human dose strength
- pKa of test compound
- Molecular mass (exact mass) of test compound and its salt form
- MSDS or handling and storage information, e.g., light-sensitive, store at -20°C, etc.
- Solubility of test compound at two pH values specified by the customer between 1.0 and 7.4
- Preliminary BCS solubility classification
- Test compound dissolved in an appropriate dosing vehicle
- 1.5 mL shake flask
- Three independent determinations (N=3)
- Combine test compound with aqueous buffers then vortex solution for circa 2 hours
- Let solution sit for at least 8 hours at 37°C
- Inspect visually for undissolved powder
- As needed filter the solution
- Prepare duplicate (N=2) samples for injection into the LC/MS/MS
- Determine the concentration of test compound using a generic LC-MS/MS method with a minimum 4-point calibration curve
- In this assay it is not determined when and if a saturated solution is obtained. Because of this the solubility value obtained might not be the true equilibrium solubility of the test compound.
- In this assay neither the recovery nor the stability of the test compound is determined.
- Unless told otherwise by the customer it is assumed that the test compound is 100% pure.The assay is often done in conjunction with EA903, Preliminary BCS Permeability.
- The customer must specify:
• either the standard or custom report format
• the two pH at which the solubility is measured—typically 2.0 and 7.4
• the buffer systemThe customer can request additional replicates