Measurement uncertainty in the analysis of antibiotics

Abstract

Many important decisions are based on the analytical data of quality control department and it is important to have indication of the quality of this results. One useful measure of this is measurement uncertainty. The uncertainty on the results may arise from many possible sources, including sampling, matrix effects and interferences, environmental conditions, uncertainties of mass and volumetric equipment, uncertainties of spectrophotometric and chromatographic equipment, uncertainties of biological and microbiological responses, purity of reagents and chemical reference substances, method validation and random variability. This work aims to establish a procedure for measurement uncertainty estimation in the analysis of amoxicillin trihydrate, amoxicillin capsules and amoxicillin for oral suspension. We will evaluation the tests and assays described in the Brazilian and American pharmacopeias, including pH test, water by Karl Fischer, assay of amoxicillin by iodometric method, assay of amoxicillin by HPLC and microbiological assay of amoxicillin by agar diffusion method. The main sources of uncertainty will be identified, their components will be quantified and converted to standard deviations in order to calculated the combined and expanded uncertainties. When relevant, the procedure for uncertainty estimation will be verified/validated by Monte Carlo simulations. The measurement uncertainty is useful in the evaluation of compliance of pharmaceutical in-process or final products, in pharmaceutical equivalence and stability studies. (AU)