A Total Error Approach for the Validation of Quantitative Analytical Methods

Abstract

Current ad-hoc approaches to method validation are inconsistent with ensuring method suitability. A total error approach based on the use of two-sided beta-content tolerance intervals was developed. The total error approach offers a formal statistical framework for assessing analytical method performance. The approach is consistent with the concept of method suitability and controls the risk of incorrectly accepting unsuitable analytical methods.

Quantitative and qualitative profiling of endocannabinoids in human plasma using a triple quadrupole linear ion trap mass spectrometer with liquid chromatography

“…As shown in Fig. 4, the accuracy profiles are included between an acceptance limit fixed at 20% [− λ , + λ ] for each concentration level which is acceptable for a bioanalytical method when a β risk is used 36, 37…”

Large-scale retrospective evaluation of regulated liquid chromatography–mass spectrometry bioanalysis projects using different total error approaches

“…␤-expectation approach (SFSTP) [10], ␤-content approach (Hoffman and Kringle) [11,12], measurement uncertainty approach (Saffaj and Ihssane) [13,14], and risk profile approach (Dewé and Hubert et al) [15]. Due to space limitation and considering the main purpose of this article, the detailed principle and formulae for the aforementioned total error approaches are not given here.…”

“…To overcome the drawbacks of the conventional approach, different approaches based on total error concept (precision and trueness combined) have been proposed [9][10][11][12][13][14][15], including ␤-expectation approach by the Société Franç aise des Sciences et Techniques Pharmaceutiques (SFSTP) [10], ␤-content approach by Hoffman and Kringle [11,12], ␤-content and measurement uncertainty approach by Saffaj and Ihssane [13,14], and risk profile by Dewé et al [15]. However, disagreements exist regarding their respective effectiveness/usefulness.…”

Method validation across the disciplines—Critical investigation of major validation criteria and associated experimental protocols

“…The importance of estimating total error is nowadays also recognized in other application fields [4,[46][47][48][49], however, it has not yet entered into the respective guidelines. One of the reasons is that the statistical concepts for acceptable total error are complex and that, currently, no generally accepted concept for statistical treatment of total error exists.…”

“…Other approaches are based on the so-called accuracy profile constructed by use of the ␤-expectation tolerance interval [47,49,63,64]. This approach, however, is still under development and regularly refined [46,65,66]. Boiled down, the concepts recommend to consider ␣-and ␤-errors and tolerance intervals in method validation studies.…”