In-line Fourier transform mid-infrared spectroscopy (FTIR) was used to monitor a reaction which had a highly inconsistent rate due to sensitivity to changes in process parameters and the quality of the starting materials. Accurate determination of the endpoint in real time was needed to prevent formation of an impurity by degradation of the product. A moving window t-test algorithm was used to predict and determine the endpoint by analysis of FTIR trends during the reaction. The method was selected because it determined the endpoint in the correct range for reactions with different process parameters and data collected with different FTIR instruments. During development, the FTIR and t-test algorithm were used to monitor reactions for feasibility studies, process optimization, use tests, robustness DoE, and scale up to pilot plant. The method for monitoring the reaction may be useful in a GMP manufacturing environment where sampling and analysis are time consuming.

中文翻译：

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一种使用原位时程数据的移动窗口t检验实时检测反应终点的方法

在线傅里叶变换中红外光谱法（FTIR）用于监测由于对工艺参数变化和原料质量的敏感性而导致速率极不一致的反应。需要实时准确地确定终点，以防止由于产品降解而形成杂质。通过分析反应期间的FTIR趋势，使用移动窗口t检验算法来预测和确定终点。选择该方法的原因是，它确定了在正确范围内的终点，该终点范围适用于使用不同工艺参数的反应以及使用不同FTIR仪器收集的数据。在开发过程中，FTIR和t-test算法用于监视反应，以进行可行性研究，过程优化，使用测试，鲁棒性DoE，并扩大规模以进行试验工厂。用于监测反应的方法在采样和分析非常耗时的GMP生产环境中可能很有用。