Departamento de Farmácia, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, Av. Prof. Lineu Prestes 580, 05508-000 São Paulo, Brazil.
Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Edifício C8, Campo Grande, 1749-016 Lisboa, Portugal.
Talanta. 2019 May 1;196:174-181. doi: 10.1016/j.talanta.2018.12.021. Epub 2018 Dec 18.
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.
对某些项目（如药品、食品或饮用水）的一致性评估，涉及使用多分析物测量程序来确定这些成分的限量。由于这些测定涉及到相关分析步骤的共享，例如样品制备和分析仪器的运行，因此各种成分的测量结果是相关的（即“成分之间具有计量相关性”）。各成分值与各自的公差限制、测量不确定度以及测量结果的相关性接近程度，会影响被分析项目的错误一致性决定的风险。这种相关性可以增加或降低错误一致性决定的风险，并且与决定该项目是否应被视为符合或不符合法规有关。这项工作提出了一种估计分析项目结果的“成分之间计量相关性”的方法，该方法随后用于评估这种相关性对错误一致性决定风险的影响。该方法成功地应用于评估药品片剂对拉米夫定（3TC）和齐多夫定（AZT）的公差限制的一致性，这些限制是从同一 HPLC-UV/Vis 运行中分析相同分析部分得出的。测量结果的相关性是通过共享分析操作的蒙特卡罗模拟确定的（线性相关系数为 0.53），其对一致性决策的影响是相关的。例如，对于测量结果分别等于上限和下限的 3TC 和 AZT，错误接受药品的风险为 84%，而如果假设测量结果是独立的，则错误地认为该风险为 75%。用于此评估的 Excel®电子表格可作为补充材料提供。
