Fiber-optic UV/visible composition monitoring for process control of batchreactions

In this paper, a method for characterizing an industrially significant reac tion using chemometrics, fiber-optic UV/visible spectroscopy and a single f iber transmission probe is reported. Aliquots of the reaction mixture were also taken at constant intervals for off-line HPLC analysis. HPLC peak area s were used to develop multivariate calibrations for the real-time determin ation of product and consumption of reactants. Composition profiles and pur e component spectra of the reactant mixture, intermediate, and product were estimated using automatic window factor analysis (WFA), a type of self-mod eling curve resolution (SMCR), without the aid of referee methods of analys is or standards. Window edges were automatically refined by a new iterative process that uses a robust adaptive noise threshold in the stopping criter ion. Strong evidence for the formation of a reactive intermediate was detec ted and characterized by SMCR that could not be detected by HPLC. Eight rep licate runs over a period of 3 months demonstrated that the SMCR results we re reproducible. Robust smoothing of the SMCR profiles with locally weighte d scatter plot smoothing (LOWESS) was used to construct control charts for detecting upsets in the batch reaction caused by the introduction of small amounts of water. Residuals (smooth-unsmoothed) outside control limits (3 x MAD, median absolute deviation of residuals from pre-run batches) Even use d to detect small, sudden process upsets. (C) 1999 Elsevier Science B.V. Al l rights reserved.