Abstract: To establish a mathematical model for rapid determination of 2 effective constituents in cold drugs, i.e., acetaminophen (AAP) and pseudoephedrine hydrochloride (PEPD), multiwavelength UV spectra of the 2 compounds were collected respectively, from which database of standard spectra (v1 and v2) of these 2 compounds were obtained. And at the same time, multiwavelength chromatograms of 4 cold drugs obtained from the market were collected separately by UV spectroscopy and HPLC in hyphenation in solutions prepared by dissolving 1 piece each of the 4 drug tablets, and data of the multiwavelength chromatograms were then transformed into values of absorbances (A) under whole wavelength at various moments. Values of absorbances of those substances having their retention times same as the analyte were subtracted from the values of A, and the data matrix not involving the constituent to be determined was obtained. And thence, after chemometric treatment by principle component analysis and resolution of unusual values, matrix database of N1 not containing AAP, and also the matrix database of N2 not containing PEPD were obtained. In the analysis of unknown samples of the drugs, one piece of each of the drugs was taken and dissolved as prescribed. Two aliquots were taken from each sample solution, one for collecting the UV spectroscopic data and the other for HPLC analysis. Spectra database a of the sample was established based on the data obtained. Results of contents of AAP and PEPD were found by using the algorithm of vector deduction. Values of RSDs (n=5) found for AAP were less than 2.0%, and for PEPD were less than 4.0%. Values of recovery found by standard addition method were in the ranges of 94.5% to 106% and 92.1% to 108% respectively. Values of the results of AAP and PEPD found by the present method were checked by the HPLC method, relative deviations between values of the 2 constituents determined by the 2 methods were within ±4.0% and ±3.0% respectively.