Quantitative Estimation of Tegafur and Uracil in Capsule Dosage Form Using Statistical Modeling Assisted Analytical Methods

ABSTRACT:This research is focused on creating robust multivariate statistical regression models, specificallyPrincipal Component Regression (PCR) and Partial Least Squares Regression (PLS), to accuratelypredict the concentrations of Tegafur and Uracil in capsule formulations. The goal was to developreliable and efficient models for simultaneous estimation of these two components.Tegafur andUracil are commonly used to treat colorectal cancer. This study employed UV-spectrophotometrycombined with chemometric techniques for accurate drug estimation. Calibration curves for bothdrugs were constructed using methanol as a solvent at a maximum UV absorption at 270 nm forTegafur and 258 nm for Uracil. Various synthetic mixtures of these drugs, within the concentrationrange of 3–18 μg/mL, were prepared and these mixtures were divided in to calibration andvalidation sets to develop the chemometric models. Spectral data from these mixtures wereprocessed using Unscrambler X software, and PCR and PLS models were developed. These modelswere used to predict the content of the drugs in Luporal capsules, a marketed formulation. Bothdrugs showed excellent linearity with R2 values above 0.999 in the specified concentration range.The relationship between the concentration of the drugs and their spectral data was found to behighly linear, with a strong correlation coefficient (R2 > 0.999) within the specified range. For thepurpose of developing a chemometric model, a specific wavelength range (225–300 nm) with a 5nm interval was chosen. The optimal number of factors for both PCR and PLS models wasidentified as 7. To assess the performance of these models, statistical metrics such as the root meansquare error of cross-validation and the root mean square error of calibration were employed, whichconfirmed the models' accuracy in predicting drug concentrations. When applied to Luporalcapsules, the models predicted the content of Tegafur and Uracil accurately, with assay values of99.44% and 101.77% (PCR) and 98.73% and 102.30% (PLS). The PCR and PLS methodsdeveloped in this study were proven to be accurate, precise, and robust for the simultaneousanalysis of Tegafur and Uracil in pharmaceutical formulations. These methods offer a reliableapproach for routine quality control testing in the pharmaceutical industry.