One of our customers, a virtual pharma, worked with us on an advancing lead. With two acidic functions it was and was highly water soluble except in strong acid, making profiling solubility across the gut tricky. They needed a solubility assay from pH 1 to pH 8 from 100 ug to 100 mg/mL. Buffers were deemed impractical due to the high concentrations (>1M) likely to change solubilty.
We decided the problem had a solution – not an automated, one-size-fits-all assay, but a solution nonetheless.
- Averica developed a low volume titration, acidifying a 100 mg/mL solution
- At the first pKa the compound started to precipitate, and at the second it precipitated heavily
- We sampled and filtered 20 uL aliquots
- Filtrate samples were analyzed by HPLC for remaining compound in solution