Sustained prediction ability of net analyte preprocessing methods using reduced calibration sets. Theoretical and experimental study involving the spectrophotometric analysis of multicomponent mixtures

Abstract

A newly developed multivariate method involving net analyte preprocessing (NAP) was tested using central composite calibration designs of progressively decreasing size regarding the multivariate simultaneous spectrophotometric determination of three active components (phenylephrine, diphenhydramine and naphazoline) and one excipient (methylparaben) in nasal solutions. Its performance was evaluated and compared with that of partial least-squares (PLS-1). Minimisation of the calibration predicted error sum of squares (PRESS) as a function of a moving spectral window helped to select appropriate working spectral ranges for both methods. The comparison of NAP and PLS results was carried out using two tests: (1) the elliptical joint confidence region for the slope and intercept of a predicted versus actual concentrations plot for a large validation set of samples and (2) the D-optimality criterion concerning the information content of the calibration data matrix. Extensive simulations and experimental validation showed that, unlike PLS, the NAP method is able to furnish highly satisfactory results when the calibration set is reduced from a full four-component central composite to a fractional central composite, as expected from the modelling requirements of net analyte based methods.