Reliability and uncertainty in the estimation of pK a by least squares nonlinear regression analysis of multiwavelength spectrophotometric pH titration data
Reliability and uncertainty in the estimation of pK a by least squares nonlinear regression analysis of multiwavelength spectrophotometric pH titration data
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DOI：
10.1007/s00216-006-0993-1
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发表时间：
2007-02-01
影响因子：
4.3
通讯作者：
Vrana, Ales
中科院分区：
文献类型：
--
作者：
Meloun, Milan;Syrovy, Tomas;Vrana, Ales
当药物溶解度差时，可以使用pH-分光光度滴定法代替电位滴定法测定解离常数，并沿着吸光度响应面数据的非线性回归。通常，回归模型对于从多波长数据集中提取基本特征非常有用。回归诊断表示用于检查回归三元组（数据、模型、方法）的程序，以便检查（a）所提出的模型的数据质量;（B）给定数据集的模型质量;以及（c）用于最小二乘法的所有假设都成立。在数据、模型和估计方法的交互式PC辅助诊断中，数据质量的检查涉及检测影响点、离群值和高杠杆，这在回归拟合吸光度响应超平面时会导致许多问题。所有面向图形的技术都适用于影响点的快速估计。酸性药物水飞蓟宾的离解常数的可靠性可以用多波长分光光度pH滴定数据的拟合优度检验来证明。本文计算了用吸收光谱的最小二乘非线性回归分析法测定弱酸pK（a）的不确定度。该程序考虑了pH测量的漂移、光谱测量的漂移和分析操作中的所有漂移，以及每个不确定度来源的相对重要性。本例实验装置中最重要的不确定性来源是pH测量的不确定性。以用SQUAD（84）和SPECFIT/32回归程序计算水飞蓟宾的混合解离常数为例，讨论了各种不确定度对准确度和精密度的影响。
When drugs are poorly soluble then, instead of the potentiometric determination of dissociation constants, pH-spectrophotometric titration can be used along with nonlinear regression of the absorbance response surface data. Generally, regression models are extremely useful for extracting the essential features from a multiwavelength set of data. Regression diagnostics represent procedures for examining the regression triplet (data, model, method) in order to check (a) the data quality for a proposed model; (b) the model quality for a given set of data; and (c) that all of the assumptions used for least squares hold. In the interactive, PC-assisted diagnosis of data, models and estimation methods, the examination of data quality involves the detection of influential points, outliers and high leverages, that cause many problems when regression fitting the absorbance response hyperplane. All graphically oriented techniques are suitable for the rapid estimation of influential points. The reliability of the dissociation constants for the acid drug silybin may be proven with goodness-of-fit tests of the multiwavelength spectrophotometric pH-titration data. The uncertainty in the measurement of the pK (a) of a weak acid obtained by the least squares nonlinear regression analysis of absorption spectra is calculated. The procedure takes into account the drift in pH measurement, the drift in spectral measurement, and all of the drifts in analytical operations, as well as the relative importance of each source of uncertainty. The most important source of uncertainty in the experimental set-up for the example is the uncertainty in the pH measurement. The influences of various sources of uncertainty on the accuracy and precision are discussed using the example of the mixed dissociation constants of silybin, obtained using the SQUAD(84) and SPECFIT/32 regression programs.