On-Line Application of Near-Infrared Spectroscopy for Monitoring Water Levels in Parts per Million in a Manufacturing-Scale Distillation Process

Abstract

An on-line analytical method based on transmission near-infrared spectroscopy (NIRS) for the quantitative determination of water concentrations (in parts per million) was developed and applied to the manufacture of a pharmaceutical intermediate. Calibration models for water analysis, built at the development site and applied at the manufacturing site, were successfully demonstrated during six manufacturing runs at a 250-gallon scale. The water measurements will be used as a forward-processing control point following distillation of a toluene product solution prior to use in a Grignard reaction. The most significant impact of using this NIRS-based process analytical technology (PAT) to replace off-line measurements is the significant reduction in the risk of operator exposure through the elimination of sampling of a severely lachrymatory and mutagenic compound. The work described in this report illustrates the development effort from proof-of-concept phase to manufacturing implementation.

Process Pattern-Based Near-Infrared Spectroscopy (NIRS) Fault Detection Using a Potential Function

“…6 Moreover, NIR spectroscopy measurement technology is used for product quality inspection and analysis as well as fault detection (FD) and status monitoring of industrial processes. 7–9…”

“…6 Moreover, NIR spectroscopy measurement technology is used for product quality inspection and analysis as well as fault detection (FD) and status monitoring of industrial processes. [7][8][9] The use of NIR spectroscopy for FD in industrial processes is currently based on multivariate statistical process monitoring (MSPM). 10,11 This technology is characterized by multiprojection and multivariate control chart.…”