title: Usefulness of capability indices in the framework of analytical methods validation.
abstract: 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.
authors.affiliation: Analytical Chemistry Laboratory, CIRM, Institute of Pharmacy, University of Liège, Liège, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Bouabidi
authors.forename: E
authors.initials: E
authors.lastname: Ziemons
authors.forename: R
authors.initials: R
authors.lastname: Marini
authors.forename: C
authors.initials: C
authors.lastname: Hubert
authors.forename: M
authors.initials: M
authors.lastname: Talbi
authors.forename: A
authors.initials: A
authors.lastname: Bouklouze
authors.forename: H
authors.initials: H
authors.lastname: Bourichi
authors.forename: M
authors.initials: M
authors.lastname: El Karbane
authors.forename: B
authors.initials: B
authors.lastname: Boulanger
authors.forename: Ph
authors.initials: P
authors.lastname: Hubert
authors.forename: E
authors.initials: E
authors.lastname: Rozet
mesh_terms: D000086:Acetazolamide / Q000032:analysis; D002623:Chemistry Techniques, Analytical / Q000379:methods* / Q000592:standards*; D002853:Chromatography, Liquid / Q000379:methods; D003198:Computer Simulation; D004345:Drug Industry / Q000379:methods / Q000592:standards / Q000639:trends; D015725:Fluconazole / Q000032:analysis; D009010:Monte Carlo Method; D004364:Pharmaceutical Preparations / Q000032:analysis*; D015203:Reproducibility of Results; D013607:Tablets / Q000737:chemistry; D054928:Validation Studies as Topic
chemical_list: D004364:Pharmaceutical Preparations; D013607:Tablets; D015725:Fluconazole; D000086:Acetazolamide