The quantitative resolution of a quaternary pharmaceutical mixture consisting of paracetamol, propiphenazone, caffeine and thiamine was performed by the simultaneous use of fractional wavelet transform (FWT) with principal component regression (PCR), partial least squares (PLS) and artificial neural networks (ANN) methods. A calibration set consisting of 22 mixture solutions was prepared by means of an orthogonal experimental design and their absorption spectra were recorded in the spectral range of 210.0-312.3nm and then transferred into the fractional wavelet domain and processed by FWT. The chemometric calibrations FWT-PCR, FWT-PLS and FWT-ANN were computed by using the relationship between the coefficients provided by FWT method and the concentration data from calibration set. An external validation was carried out by applying the developed methods to the analysis of synthetic mixtures of the related compounds, obtaining successful results. The models were finally used to assay the studied drugs in the commercial pharmaceutical formulations.