Models such as ordinary least squares, independent component analysis, principle component analysis, partial least squares, and artificial neural networks can be found in the calibration literature. Linear or nonlinear methods can be used to explain the structure of the same phenomenon. Each type of model has its own advantages with respect to the other. These methods are usually grouped taxonomically, but different models can sometimes be applied to the same data set. Taxonomically, ordinary least square and artificial neural network use completely different analytical procedures but are occasionally applied to the same data set. The aim of the study of methodological superiority is to compare the residuals of models because the model with the minimum error is preferred in real analyses. Calibration models, in general, are based on deterministic and stochastic parts; in other words, the data are equal to the model + the error. Explaining a model solely using statistics such as the coefficient of determination or its related significance values is sometimes inadequate. The errors of a model, also called its residuals, must have minimum variance compared to its alternatives. Additionally, the residuals must be unpredictable, uncorrelated, and symmetric. Under these conditions, the model can be considered adequate. In this study, calibration methods were applied to the raw materials, hydrochlorothiazide and amiloride hydrochloride, of a drug, as well as a sample of the drug tablet. The applied chemical procedure was fast, simple, and reproducible. The various linear and nonlinear calibration methods mentioned above were applied, and the adequacy of the calibration methods was compared according to their residuals.