The dissociation constant pK_a of the Roxadustat with UV-VIS spectra, molar absorption coefficients and protonation equilibria are the key physicochemical parameters influencing many biopharmaceutical characteristics. Roxadustat is an orally bioavailable, hypoxia-inducible factor prolyl hydroxylase inhibitor with potential anti-anemic activity. It belongs to Active Pharmacenutical Ingredients, which have acidic/basic functionalities, their ionization state is controlled by solution pH and acid dissociation constants. Nonlinear regression of the pH-spectra with programs REACTLAB and SQUAD84 and of the pH-titration curve with ESAB determined four multiple consecutive dissociation constants with the protonation scheme. A sparingly soluble neutral molecule LH₃ of Roxadustat was dissociated to the soluble anions LH₂⁻, LH²⁻ and L³⁻ or protonated to the cation LH₄⁺ in an aqueous medium. The graph of molar absorption coefficients of variously protonated species according to wavelength shows that the spectra of two anions LH₂⁻ and LH²⁻ are nearly the same in colour. The Roxadustat spectrum exhibited five sharp isosbestic points, which were related to the LH²⁻/L³⁻ equilibrium. Four consecutive thermodynamic dissociation constants were estimated using UV-metric data pK^T_a1 = 3.60(04), pK^T_a2 = 5.62(14), pK^T_a3 = 7.66(16), pK^T_a4 = 9.08(02) at 25 °C and pK^T_a1 = 3.60(04), pK^T_a2 = 5.73(10), pK^T_a3 = 7.52(10), pK^T_a4 = 8.99(02) at 37 °C and using pH-metric data pK^T_a1 = 4.33(09), pK^T_a2 = 6.57(11), pK^T_a3 = 8.88(05), pK^T_a4 = 9.03(04) at 25 °C and pK^T_a1 = 4.25(09), pK^T_a2 = 6.49(10), pK^T_a3 = 8.80(06), pK^T_a4 = 9.00(05) at 37 °C The positive values of the enthalpy ΔH⁰ showed that the dissociation process is endothermic and the positive values of the Gibbs free energy ΔG⁰ at 25 °C indicated that the dissociation process was not spontaneous, which also was confirmed by a negative value of the entropy ΔS⁰. Four macro-dissociation constants of Roxadustat and six protonation locations were predicted by MARVIN.

Roxadustat的解离常数p K _a与UV-VIS光谱，摩尔吸收系数和质子化平衡是影响许多生物制药特性的关键物理化学参数。Roxadustat是一种口服生物可用的低氧诱导因子脯氨酰羟化酶抑制剂，具有潜在的抗贫血活性。它属于活性药物成分，具有酸性/碱性功能，其电离状态由溶液的pH值和酸解离常数控制。使用REACTLAB和SQUAD84程序对pH光谱进行非线性回归，使用ESAB进行pH滴定曲线的非线性回归，确定了质子化方案的四个连续解离常数。难溶的中性分子LH ₃的Roxadustat被离解以可溶性阴离子LH ₂ ^-，LH ^2-和L ^3-或质子化以阳离子LH ₄ ⁺中的水性介质。根据波长不同地示出了质子化物种的摩尔吸光系数的曲线图的两个阴离子的光谱LH ₂ ^-和LH ^2-在颜色几乎相同。Roxadustat光谱显示出五个尖锐的等渗点，这些点与LH ^2- / L ^3-平衡有关。使用紫外测量数据p K ^T _a1  = 3.60（04），p K估计四个连续的热力学解离常数^T _a2  = 5.62（14），p K ^T _a3  = 7.66（16），p K ^T _a4  = 9.08（02）在25°C和p K ^T _a1  = 3.60（04），p K ^T _a2  = 5.73（10） ），p K ^T _a3  = 7.52（10），p K ^T _a4  = 8.99（02）在37°C并使用pH值数据p K ^T _a1  = 4.33（09），p K ^T _a2  = 6.57（11） ，p K ^T _a3  = 8.88（05），p K ^T _a4  = 9.03（04）在25°C和p K ^T _a1时 = 4.25（09），p K ^T _a2  = 6.49（10），p K ^T _a3  = 8.80（06），p K ^T _a4  = 9.00（05）在37°C时，焓ΔH ⁰的正值表明解离过程是吸热的，吉布斯自由能ΔG ⁰在25°C下的正值表明解离过程不是自发的，这也由熵ΔS ⁰的负值证实。MARVIN预测了Roxadustat的四个宏观解离常数和六个质子化位置。