Allen R I, Box K J, Comer J E, Peake C, Tam K Y
Sirius Analytical Instruments Ltd., Riverside, East Sussex, UK.
J Pharm Biomed Anal. 1998 Aug;17(4-5):699-712. doi: 10.1016/s0731-7085(98)00010-7.
A multiwavelength spectrophotometric approach has been developed to determine acid dissociation constants (pKa values) of sparingly soluble drug compounds. UV absorption spectra of the drug solution are acquired using a versatile device based on a fiber optics dip probe, a light source and a photodiode array (PDA) detector while the PH and the ionic strength of the chemical system is manipulated precisely by means of a commercially available titrator. Target factor analysis (TFA) has been applied to deduce the pKa values from the multiwavelength UV absorption data recorded at different pH values. We have called this multiwavelength approach the WApH technique because the pKa results are determined from changes in Wavelength and Absorbance as a function of pH (WApH). The WApH technique is exemplified by using several pure drugs, namely, niflumic acid, nitrazepam, pyridoxine, quinine and terbutaline. The pKa values obtained agree well with those derived from pH-metric titrations. It has been demonstrated that the WApH technique is able to deduce pKa values with high accuracy even if the absorption spectra of the reacting species are very similar.
已开发出一种多波长分光光度法来测定难溶性药物化合物的酸解离常数（pKa值）。使用基于光纤浸入式探头、光源和光电二极管阵列（PDA）检测器的通用设备获取药物溶液的紫外吸收光谱，同时借助市售滴定仪精确控制化学体系的pH值和离子强度。已应用目标因子分析（TFA）从在不同pH值下记录的多波长紫外吸收数据中推导pKa值。我们将这种多波长方法称为WApH技术，因为pKa结果是根据波长和吸光度随pH值的变化（WApH）来确定的。通过使用几种纯药物，即尼氟酸、硝西泮、吡哆醇、奎宁和特布他林，对WApH技术进行了举例说明。获得的pKa值与通过pH滴定法得到的值非常吻合。结果表明，即使反应物种的吸收光谱非常相似，WApH技术也能够高精度地推导pKa值。
