Measurement uncertainty of a UPLC stability indicating method for determination of linezolid in dosage forms

Abstract

Many decisions of compliance or non-compliance are based in analytical results. There are in literature several methods described for linezolid determination, however only a few takes into account the measurement uncertainty. The aim of this work was to validate, identify the main sources of uncertainty, quantify the standard deviation of each source of uncertainty, and calculated combined and expended uncertainties for the determination of linezolid in injectable dosage forms. The UPLC method was validated by assessing specificity, linearity/linear range, precision (repeatability and intermediate precision), accuracy and robustness. Eurachem procedure was used in measurement estimation and then evaluated using Monte Carlo simulations. Linezolid was degraded after exposed to light and oxidation. The UPLC method was linear (range from 8.0 to 12.0μg/mL, with r2=0.9985), showed good precision (repeatability of 0.89% and intermediate precision of 0.66%), accurate (recovery from 98.07% to 99.03%) and robust. The contributions of accuracy, precision, linearity and weight of linezolid reference standard are the most significant, contributing with about 72% of the overall uncertainty. The other sources of uncertainties have lower influence on the overall uncertainty. The uncertainty estimated by Eurachem procedure (95.13±2.51%) was found to be similar to the Monte Carlo simulation (95.14±2.46%). Measurement uncertainty was found to be appropriated for its applications.