Methods for measuring solubility
Sirius pH-metric CheqSol and Curve-Fitting solubility methods measure intrinsic solubility and kinetic solubility. This diagram shows the Intrinsic Solubility of Dipyridamole measured on the SiriusT3 instrument by the CheqSol method, with a result of 8.2 µM.
For a detailed explanation of CheqSol and Curve-fitting methods, see our 2011 Webinar on “How CheqSol works”,
available from the Library section of this website.
Using the Sirius inForm, Controlled Supersaturation experiments can be used to assess extent and duration of supersaturation. In this example the instrument was instructed to titrate to a “Target pH” just below the pH where precipitation should occur. At that pH the sample is supersaturated. The solution is then stirred and pH is recorded. The solution remains fully supersaturated until the induction time when it begins to precipitate. The duration of supersaturation and the precipitation rate can be deduced from the data.
For more information about Controlled Supersaturation, see Application note 402, available from the Library section of this website.
The solubility of ionisable compounds changes as a function of pH. This graph was created from the measured Intrinsic Solubility value of Dipyridamole and the measured pKa. The dark green line shows the solubility vs. pH. The weight of sample used in the experiment was 5 mg in a starting volume of 1.5 mL.
The dark green line is calculated using an equation of the type first described by Henderson and Hasselbalch. If solubility was measured by shake-flask in a buffer solution fixed pH, it would provide one point on this line, such as the example shown by the red dot at pH 6.6. It’s been shown that results from carefully performed shake-flask experiments agree very well with “Henderson-Hasselbalch” values calculated from pKa and CheqSol intrinsic solubility results:
Völgyi, G.; Baka, E.; Box, K. J.; Comer, J. E.; Takács-Novák, K., Study of pH-dependent solubility of organic bases. Revisit of Henderson-Hasselbalch relationship. Anal Chim Acta 2010, 673 (1), 40-46.