Risk of false conformity decisions of multicomponent items controlled by correlated measurement results due to the sharing of analytical steps

Publication date: 1 May 2019

Source: Talanta, Volume 196

Author(s): Felipe R. Lourenço, Ricardo J.N. Bettencourt da Silva

Abstract

The assessment of the conformity of some items, such as medicines, food products or drinking waters, with limits set for several of their components, involves the determination of these components using multi-analyte measurement procedures. Since these determinations involve the sharing of relevant analytical steps, such as the sample preparation and analytical instrument run, the measurement results of the various components become correlated (i.e. 'between components metrologically correlated'). The closeness of the values of the components to the respective tolerance limits, the measurements uncertainty and the correlation of the measurements results affects the risk of false conformity decisions of the analysed item. This correlation can either increase or decrease the risk of false conformity decision and is relevant to decide if the item should be considered conform or not conform with the regulation. This work presents a methodology to estimate the 'between components metrological correlation' of results of the analysis of an item subsequently used to assess the impact of this correlation on the risk of false conformity decisions. The methodology was successfully applied to the assessment of the conformity of pharmaceutical tablets against tolerance limits for lamivudine (3TC) and zidovudine (AZT) determined from the analysis of the same analytical portion in the same HPLC-UV/Vis run. The correlation of measurement results was determined from Monte Carlo simulations of shared analytical operation (linear correlation coefficient of 0.53) being their impact on conformity decisions relevant. For instance, for measurement results of 3TC and AZT equal to the upper limit and lower limit, respectively, the risk of a wrong acceptance of the medicines is 84% while if it is assumed that measurement results are independent this risk would be wrongly considered as 75%. The Excel® spreadsheet used for this assessment is made available as supplementary material.

Graphical abstract

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