The solubility analysis based on potentiometric principles produces results comparable to the "shake flask" technique (validated by the FDA). To perform the solubility experiments by potentiometric methods, the pK_a must be known. The experiments are performed in 0.15M KCl solution containing no buffers.

The potentiometric method has demonstrated a wide dynamic range of intrinsic solubility: 5 ng/mL to 50 mg/mL. We routinely measure intrinsic solubility between 10 ng/mL to 25 mg/mL.

Intrinsic solubility is measured and the solubility-pH profile is determined using knowledge of the pK_a. Compound salt solubility is not addressed with this technique. The solubility-pH profile is presented over the pH range that excludes the likely onset of salt precipitate.

• The pK_a must also be determined. If the pK_a cannot be determined, the solubility will not be measured
• Fill out Sample Submittal Sheet for EACH compound (can be downloaded below)
• Obtain a purchase order number and include the number on the sheet
• Send 15-20 mg (more may be required) of compound to pION.

Solubility measurements are performed at specific pH values in our laboratory using a modified shake-flask method. The compounds are diluted in aqueous, non-phosphate buffer solutions (which contain <1% by volume DMSO). For equilibrium solubility, the solutions are allowed to incubate at least 15 hours (kinetic measurements available upon request). The solutions are then filtered and quantified by a UV spectrophotometer. This technique has a lower limit of solubility at 0.1 µg/mL and an upper limit of solubility, usually between 100-200 µg/mL. Since this method does not use potentiometry, any compound with UV absorption properties may be submitted for analysis.

• Fill out Sample Submittal Sheet (can be downloaded below)
• Fill out the Sample Input Template (can be downloaded below) and email to analytical.service@pion-inc.com
• Obtain a purchase order number and include the number on the sheet
• Send 100 µL of your sample as a 10-100 mM DMSO solution in a frozen microtitre plate. Alternatively, 5-7 mg of solid may be submitted.*

* Additional sample preparation charge applies.

Sample Submittal Sheet (PDF)

Sample Input Template (XLS)

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