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pH-Metric Titration: The pH-metric method is a critical reference method because it can be used to measure all pKas between 2 and 12, with or without a UV chromophore, provided that the sample can be dissolved in water or water/co-solvent over the pH range of interest. While the pH-metric method is not fast enough for rapid screening, it provides a valuable backup for measuring samples without UV absorbance. Hybrid pH-Metric/UV Method: Multi-wavelength UV absorbance of the sample solution is monitored throughout the titration. Samples must have a chromophore, and the absorbance must change as a function of ionization. During measurement, samples are acid-base titrated across a pH range that includes the pKa(s), and multi-wavelength UV spectra are measured at each pH. The pKas are calculated using a technique based on target factor analysis (TFA) https://www.creative-bioarray.com/services/lipophilicity-and-pka-assays.htm

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