Background: Sensitivity in the determination of the drug concentration is critical in pharmaceutical analysis. This research investigates several approaches for determining two sensitivity parameters, the Limit of Detection (LOD) and the Limit of Quantification (LOQ), in the analysis of the drug concentration using High-Performance Liquid Chromatography (HPLC). Methods: The study evaluates the FDA’s Lower Limit of Quantification (LLOQ) parameter, following global standards and quantitatively comparing sensitivity parameters for an established HPLC-UV method for the analysis of carbamazepine and phenytoin. Results: The study found that the LOD and LOQ values obtained by different methods varied significantly. The signal-to-noise ratio (S/N) method provided the lowest LOD and LOQ values for both drugs, while the standard deviation of the response and slope (SDR) method resulted in the highest values. This highlights the variability in sensitivity depending on the method used. Conclusion: The results show significant differences among calculated sensitivity values, emphasizing the influence of methodological variations on sensitivity values. It recommends following FDA criteria in chromatographic-based pharmaceutical analysis to improve the accuracy of drug concentration determination.