Bernstein Michael A, Stefinović Marijan, Sleigh Chris J
AstraZeneca R&D Charnwood, Bakewell Rd, Loughborough, Leics, UK LE11 5RH.
Magn Reson Chem. 2007 Jul;45(7):564-71. doi: 10.1002/mrc.2007.
Quality assurance and process understanding are assuming increasing importance in the production of Active Pharmaceutical Ingredients (APIs). NMR has the potential to report on physical processes, quantities, structures, and speciation as chemical reactions progress. Following the progression of chemical reactions by placing the sample in an NMR tube, one can perform a large number of useful studies that provide chemical and mechanistic insight. But this simple approach can have limitations, and we have therefore constructed an apparatus comprising a laboratory reactor coupled with an NMR flow cell. The reactor duplicates the exact reaction conditions that will apply with large-scale production. This reaction mixture is sampled and pumped to a high-resolution NMR flow cell where the spectrum is recorded through the course of the reaction. We demonstrate the utility of reaction monitoring using NMR both for simple cases where tubes can be used, and describe the design of the on-flow apparatus and highlight its utility with an example.
质量保证和工艺理解在活性药物成分（API）的生产中变得越来越重要。随着化学反应的进行，核磁共振（NMR）有潜力报告物理过程、数量、结构和物种形成情况。通过将样品置于NMR管中跟踪化学反应进程，可以进行大量有用的研究，从而提供化学和机理方面的见解。但这种简单方法可能存在局限性，因此我们构建了一种装置，该装置由一个实验室反应器与一个NMR流通池相连组成。该反应器复制了大规模生产时将采用的精确反应条件。对该反应混合物进行采样并泵入高分辨率NMR流通池，在反应过程中记录光谱。我们展示了使用NMR进行反应监测在可使用试管的简单情况下的实用性，并描述了流通装置的设计，并通过一个例子突出其实用性。
