Shimizu Yoshihiko, Tamura Takahiko, Ono Masaki, Kasai Osamu, Nakajima Toshiaki
Taisho Pharmaceutical Company, Ltd., 403 Yoshino-cho 1-chome, Saitama-shi, Saitama 330-8530, Japan.
Drug Dev Ind Pharm. 2002 Sep;28(8):931-7. doi: 10.1081/ddc-120006425.
We proposed a method for objectively selecting the most fitted rate equation among candidate rate equations based on chemical kinetics by both nonlinear regression analysis and Akaike's information criterion (AIC), to express the decrease of pharmaceutical ingredient as an appropriate equation. Pseudo-zero, first, and second-order rate equations were prepared as candidates beforehand, and AIC was introduced for selecting the most fitted rate equation among the candidates. We compared the proposed method to the Weibull method that expressed any decrease patterns as a single equation. We quantified the contents of thiamine nitrate (VB1) and taurine after storage for one, three, and six months under 40 degrees C-75% relative humidity by high-pressure liquid chromatography. Decrease patterns of each sample were most fitted to one of the candidate rate equations, that is, pseudo-zero, first, and second-order rate equations, respectively, and the degree of fit in the most fitted equation was superior to that of the Weibull method, except for the pseudo-first-order rate equation. Moreover, we confirmed that the proposed method was considerably precise for estimating the stability of pharmaceuticals by comparing estimated residual rates and confidence intervals to experimental data.
我们提出了一种基于化学动力学，通过非线性回归分析和赤池信息准则（AIC），在候选速率方程中客观选择最拟合速率方程的方法，以便用一个合适的方程来表示药物成分的降解情况。预先准备了伪零级、一级和二级速率方程作为候选方程，并引入AIC来在候选方程中选择最拟合的速率方程。我们将所提出的方法与将任何降解模式表示为单个方程的威布尔方法进行了比较。我们通过高压液相色谱法对在40℃-75%相对湿度下储存1、3和6个月后的硝酸硫胺（VB1）和牛磺酸含量进行了定量。每个样品的降解模式分别最拟合于候选速率方程之一，即伪零级、一级和二级速率方程，并且除了伪一级速率方程外，最拟合方程的拟合度优于威布尔方法。此外，通过将估计的残留率和置信区间与实验数据进行比较，我们证实了所提出的方法在估计药物稳定性方面相当精确。
