A method for the determination of 1-hydroxypyrene in urine and hexachlorbenzene in water applying the regression triplet in the calibration procedure of chromatographic data has been applied. The detection limit and quantification limit are currently calculated on the basis of the standard deviation of replicate analyses at a single concentration. However, since the standard deviation depends on concentration, these single-concentration techniques result in limits that are directly dependent on spiking concentration. A more rigorous approach requires first careful attention to the three components of the regression triplet (data, model, method), examining (1) the data quality of the proposed model, (2) the model quality and (3) the least-squares method to be used for fulfilment of all least-squares assumptions. For high-performance liquid chromatography determination of 1-hydroxypyrene in urine and gas chromatography analysis of hexachlorbenzene in water, this paper describes the effects of deviations from five basic assumptions The paper considers the correction of deviations: identifying influential points, namely, outliers, the calibration task depends on the regression model used, and the least-squares method is based on the assumptions of the normality of the errors, homoscedasticity and the independence of errors. Results show that the approach developed provides improved estimates of analytical limits and that the single-concentration approaches currently in wide use are seriously flawed.