Using measurement uncertainty to assess the fitness for purpose of an HPLC analytical method in the pharmaceutical industry

Chromatographic methods are widely used in pharmaceutical industry to assess quality, safety and efficacy of drug products. We found in literature a few number of works regarding the estimation of measurement uncertainty associated with chromatographic methods, however none of them evaluated whether the measurement uncertainty estimation values are reasonable to be applied in conformity assessment. Because of uncertainty in measurement, there is always the risk of incorrectly deciding whether or not a lot conforms to its specified requirement. In this paper, the measurement uncertainty associated with high performance liquid chromatography (HPLC) assay of amoxicillin 500 mg tablets were estimated, as well as the assessment of process capability and statistical process control of its industrial manufacturing process. In addition, consumer and producer's risks were estimated using Monte Carlo simulation. The manufacturing process was under control, but considering the measurement uncertainty, there was a considerable number of lots that may be out-of-specification. Based on Monte Carlo simulation, it was noticed that the producer's risk was significantly higher than consumer's risk. In addition, overall uncertainty and tolerance ratio was found to be higher than the recommended value. In other words, this assay cannot be deemed fit-for-purpose.