Study of preprocessing methods for the determination of crystalline phasesin binary mixtures of drug substances by X-ray powder diffraction and multivariate calibration

In this paper, various preprocessing methods were tested on data generated by X-ray powder diffraction (XRPD) in order to enhance the partial least-sq uares (PLS) regression modeling performance, The preprocessing methods exam ined were 22 different discrete wavelet transforms, Fourier transform, Savi tzky-Golay, orthogonal signal correction (OSC), and combinations of wavelet transform and OSC, and Fourier transform and OSC. Root mean square error o f prediction (RMSEP) of an independent test set was used to measure the per formance of the various preprocessing methods. The best PLS model was obtai ned with a wavelet transform (Symmlet 8), which at the same time compressed the data set by a factor of 9.5. With the use of wavelet and X-ray powder diffraction, concentrations of less than 10% of one crystal from could be d etected in a binary mixture. The linear range was found to be in the range 10-70% of the crystalline form of phenacetin, although semiquantitative wor k could be carried out down to a level of approximately 2%. Furthermore, th e wavelet-pretreated models were able to handle admixtures and deliberately added noise.