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Objective: In order to solve the problem that there is no conclusive report of the dissociation constant of tofacitinib citrate, the dissociation constant of tofacitinib citrate was determined for the first time by using the model algorithm of different dissociation constants of ultraviolet spectroscopy. It provides an important reference for the analysis and design of the drug form. Methods: The characteristic absorption wavelengths of tofacitinib citrate were obtained by scanning the pH gradient solutions of different tofacitinib citrate by ultraviolet spectroscopy, and the dissociation constant of tofacitinib citrate was calculated according to the logarithmic value of the absorbance ratio of the molecular tofacitinib citrate and the ionized tofacitinib citrate and the data of pH calculation. At the same time, the ionization hop in the acidic environment is derived according to the relationship between the absorbance ratio and pH of the selected different reference wavelengths and the main characteristic absorption wavelength, and the pH value of the ionic and molecular states is the dissociation constant. Results: The dissociation constant of tofacitinib citrate under acidic conditions was 6.0. In addition, the pKa of the substance was calculated according to the structural formula of tofacitinib citrate using commercial dissolution constant estimation software, which was close to the experimental results. The accuracy of the results is corroborated. Buffer test samples corresponding to pH were prepared, and the results were well analyzed. Conclusion: The method of determining the dissociation constant of weak acid and weak base salt - tofacitinib citrate by ultraviolet spectroscopy is simple and fast, and the determination results are reliable.
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Jinxiang et al. (2024) studied this question.
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