On-Line Process Control of Liquid Chromatography

Abstract

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.

On-Line Process Control of Gradient Elution Liquid Chromatography

“…Chemometric Model ing. In the previously reported isocratic LCPC system, the elution phase was considered a fairly static process and continuously treated with principal component analysis (PCA). In this example, however, the elution phase is not static but dynamic since the mobile-phase composition changes during the run.…”

“…It is not uncommon that every second injection is a reference solution. In a previous report, 1 we presented an alternative approach to monitor LC system stability during the actual run. The liquid chromatography process control (LCPC) system entails monitoring of certain key apparatus-related physical parameters, such as pressures, temperature, and conductivity of the mobile phase, in combination with multivariate statistical process control (MSPC).…”

“…sequence, thus creating a continuous system suitability test. It was argued 1 that not only can the number of reference solution injections potentially be reduced, process monitoring of the analytical system also enables an improved quality of the data obtained. However, the approach was at the time limited to isocratic runs, whereas many LC methods are performed in the gradient mode.…”