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The pKa determination by UV titration relies on the differences in molar absorptivity between charged and uncharged species present in solution[1]. The traditional UV titration of a compound takes about 25–30 minutes. The fast UV titration method utilizes Pion’s linear universal buffer Prisma™ HT. It enables replacing a variable volume titrant addition with a constant volume addition that produces predictable pH change with each dispensed aliquot of KOH or HCl. This technical note demonstrates that reducing the number of titration points while keeping their uniform distribution along pH axis produces comparable results to the regular UV titrations while reducing the assay time to 7–10 minutes per titration. Additional potential benefit of fast titrations is that low-soluble compounds can stay supersaturated for a short period of time. That may enable aqueous pKa measurements for some low-soluble compounds that otherwise have to be determined only with the presence of cosolvent. It can also benefit compounds that are not stable and would decompose during the long assay.

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