he calibration set and prediction set were configured according to the central composite design,then PLS and PCR were applied on zero and first order derivative spectra of the mixture of three components——aspirin,paracetamol and salicylic acid.And the derivative spectrophotometric multivariate calibration methods were used for the simultaneous measurement of the mixture.The results showed that the absorption spectra of aspirin,paracetamol and salicylic acid overlapped seriously.Derivative ratio spectrophotometry could not simultaneously measure the content of each component in the mixture since the zero crossing points of the components overlapped.The derivative spectrophotometric multivariate calibration methods could effectively prevent the zero crossing points of the individual components from coinciding in linear range.The average relative errors of all components in the prediction set were below 3.6%,and the average recoveries were 101%.Each component of the real pharmaceutical samples also had exact prediction results.With good sensitivity and the limit of detection,the derivative spectrophotometric multivariate calibration methods could be used to measure simultaneously the contents of the three components in drug synthesis and quality inspection.