This work describes a very simple, novel and selective spectrophotmetric method for simultaneous determination of sulfamethoxazole and trimethoprim in pharmaceutical preparation and synthetics samples using direct orthogonal signal correction-partial least squares (DOSC-PLS). The all factors affecting on the sensitivity were optimized and the linear dynamic range for determining of these drugs was found. The PLS modeling was used for the multivariate calibration of the spectrophotometric data and DOSC was used for preprocessing of data matrices and the prediction results of model. The experimental calibration matrix was designed by measuring the absorbance over the range 200-400 nm for 32 samples of 2.0-15.0 and 0.4-6.0 μg mL-1 of sulfamethoxazole and trimethoprim, respectively. The root mean square error of prediction for sulfamethoxazole and trimethoprim using DOSC-PLS and PLS were 0.02212, 0.02363 and 0.17014, 0.01660,μg mL-1 respectively. Application of the method to synthetic samples of standard solutions and in pharmaceutical formulation was performed and satisfactory results were obtained.
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