On-line process control of liquid chromatography

Many analytical methods are based on liquid chromatography and typically the only measure of system stability is standards, injected repeatedly throughout the sequence. In this paper, a novel approach is presented, where the analytical run is treated as a process with the chromatographic data as the product. It is postulated that enhanced quality of the data can be obtained through monitoring the process, i.e., the chromatographic system, during the sequence. For this purpose, a liquid chromatography process control (LCPC) system has been developed. Here, several parameters, e.g., the pressure at the column and the injection valve, are monitored. Chemometrics is used for interpreting the data and producing multivariate statistical process control (MSPC) charts. The chromatographic run is divided into two parts: the dynamic injection phase and the static elution phase. Two principal component analysis (PCA) models, one for each phase, are continuously created and upgraded as the data are collected. The results of the PCA are shown in the MSPC charts, and when an error detection limit is exceeded, the analyst is promptly notified. LCPC, a continuous system suitability test, provides better control of the analysis, allowing a reduction in the number of standards and replicates. Furthermore, troubleshooting is facilitated.