The transfer of a multivariate calibration model for quantitative determination of diethylene glycol (DEG) contaminant in pharmaceutical-grade glycerin between five portable Raman spectrometers was accomplished using piecewise direct standardization (PDS). The calibration set was developed using a multi-range ternary mixture design with successively reduced impurity concentration ranges. It was found that optimal selection of calibration transfer standards using the Kennard–Stone algorithm also required application of the algorithm to multiple successively reduced impurity concentration ranges. Partial least squares (PLS) calibration models were developed using the calibration set measured independently on each of the five spectrometers. The performance of the models was evaluated based on the root mean square error of prediction (RMSEP), calculated using independent validation samples. An F-test showed that no statistical differences in the variances were observed between models developed on different instruments. Direct cross-instrument prediction without standardization was performed between a single primary instrument and each of the four secondary instruments to evaluate the robustness of the primary instrument calibration model. Significant increases in the RMSEP values for the secondary instruments were observed due to instrument variability. Application of piecewise direct standardization using the optimal calibration transfer subset resulted in the lowest values of RMSEP for the secondary instruments. Using the optimal calibration transfer subset, an optimized calibration model was developed using a subset of the original calibration set, resulting in a DEG detection limit of 0.32% across all five instruments.
Connie M. Gryniewicz-Ruzicka, Sergey Arzhantsev, Lindsey N. Pelster, Benjamin J. Westenberger, Lucinda F. Buhse, and John F. Kauffman, "Multivariate Calibration and Instrument Standardization for the Rapid Detection of Diethylene Glycol in Glycerin by Raman Spectroscopy," Appl. Spectrosc. 65, 334-341 (2011)