Evaluating the measurement uncertainty in content determination of paracetamol granules by ultraviolet spectrophotometry

Abstract

An evaluation was conducted to assess the measurement uncertainty in determining paracetamol content in granules using UV spectrophotometry, a common pharmaceutical quality control method. While the principles of uncertainty calculation are established, this study provides a detailed, practical application for this specific widely used pharmacopoeial assay. The process involved identifying uncertainty sources from the analytical procedure, including sample weighing (W_s), average pack weight (W), volumetric dilutions using 100 mL flasks (V₁, V₃) and a 5 mL pipette (V₂), absorbance measurement (A) at 257 nm, and the specific absorbance value \({\text{E}}_{\text{1 cm}}^{\text{1\%}}\). Individual uncertainty components were quantified based on instrument tolerances (balance, spectrophotometer, glassware) and temperature effects, following a cause-and-effect analysis and Eurachem guidelines. Measurement repeatability (RSD) was also incorporated. The combined standard uncertainty and expanded uncertainty (k = 2) were calculated using established formulas and spreadsheet methods. Results showed the average paracetamol content was determined to be 100.14%. For a single determination, the expanded uncertainty was 6.13%. Major contributors were identified as measurement repeatability, the uncertainty of the specific absorbance value, and volumetric steps. Performing the determination in triplicate significantly reduced the repeatability contribution, lowering the overall expanded uncertainty to 4.01%, yielding a final reported result of (100.14 ± 4.01)%. This research establishes a robust procedure for uncertainty evaluation, enhancing the reliability of UV spectrophotometric assays for paracetamol granules and providing a useful framework for quality control laboratories.