Analytical Chemistry Laboratory, CIRM, Institute of Pharmacy, University of Liège, Liège, Belgium.
Anal Chim Acta. 2012 Feb 10;714:47-56. doi: 10.1016/j.aca.2011.11.019. Epub 2011 Dec 6.
Analytical methods capability evaluation can be a useful methodology to assess the fitness of purpose of these methods for their future routine application. However, care on how to compute the capability indices have to be made. Indeed, the commonly used formulas to compute capability indices such as Cpk, will highly overestimate the true capability of the methods. Especially during methods validation or transfer, there are only few experiments performed and, using in these situations the commonly applied capability indices to declare a method as valid or as transferable to a receiving laboratory will conduct to inadequate decisions. In this work, an improved capability index, namely Cpk-tol and the corresponding estimator of proportion of non-conforming results (π(Cpk-tol)) have been proposed. Through Monte-Carlo simulations, they have been shown to greatly increase the estimation of analytical methods capability in particular in low sample size situations as encountered during methods validation or transfer. Additionally, the usefulness of this capability index has been illustrated through several case studies covering applications commonly encountered in the pharmaceutical industry. Finally a methodology to determine the optimal sample size required to validate analytical methods is also given using the proposed capability metric.
分析方法能力评估可以是一种有用的方法学，用于评估这些方法在未来常规应用中的适用性。然而，需要注意如何计算能力指数。实际上，常用的计算能力指数（如 Cpk）的公式会过高估计方法的真实能力。特别是在方法验证或转移期间，通常只进行少量实验，如果在这些情况下使用常用的能力指数来声明方法有效或可转移到接收实验室，将导致不适当的决策。在这项工作中，提出了一种改进的能力指数，即 Cpk-tol 及其对应的不合格结果比例估计值（π（Cpk-tol））。通过蒙特卡罗模拟表明，它们在方法验证或转移期间遇到的低样本量情况下，极大地提高了分析方法能力的估计。此外，通过涵盖制药行业中常见应用的几个案例研究，说明了该能力指数的有用性。最后，还给出了一种使用所提出的能力度量标准确定验证分析方法所需最佳样本量的方法。
