ABSTRACT
There are numerous analytical methods that can be applied to process monitoring, and the optimal technique depends upon the physical properties most relevant to the transformation in question. For example, while gas chromatography (GC) or high-performance liquid chromatography (HPLC) would be applicable to monitoring the progress of a Diels-Alder reaction, acid titration would be more appropriate for a step in which an HCl salt is formed. In the past, analytical methods for process monitoring in the pharmaceutical industry have been predominantly indirect or “off-line” in nature. That is, they are not real-time, direct measurements of processes. Rather, they are measurements of samples taken from the process, and typically transformed into a new mixture. For example, HPLC analysis usually involves sampling and dilution prior to analysis. Although often an accurate measurement of the reaction mixture, it is not a direct analysis of the actual reaction medium. In contrast,
in situ
or real-time monitoring involves analysis of the reaction mixture directly through incorporation of the analytical measurement device into the process vessel or stream.
