An Overall Validation Approach Based on β-Content, γ-Confidence Tolerance Interval, and Uncertainty Profile: Application to LC-MS/MS Quantification of Carbendazim in Drinking Water

Abstract

Background: Carbendazim is a fungicide which can seep into the water supply, presenting a public health risk, and therefore the accurate trace determination of this substance is very important.

Objective: The purpose of the study is to take a top-down analytical validation approach in order to determine the amount of carbendazim in drinking water by using an SPE-LC-MS/MS technique.

Methods: Quantification of carbendazim using solid-phase extraction coupled with LC-MS/MS was used in order to ensure the accuracy of the analytical method and to control the risk of its routine application. An overall validation methodology based on two-sided tolerance interval type β-content, γ-confidence has been applied for the validation and estimation of uncertainty by building a decision graphical tool called the "uncertainty profile" by using the statistical process known as the Satterthwaite approximation with no recourse to additional data by satisfying intermediate precision condition for each concentration level within the acceptance limits fixed in advance.

Results: The process of validation is based on the selection of a linear weighted 1/X model enabling validation of the carbendazim dosage using LC-MS/MS in the range of working concentrations as the βγ-CCTI fell inside acceptable limits of ±10%, and the relative expanded uncertainty did not surpass 7% regardless of the β values (66.7, 80, and 90%) and the 1- γ = risk (10 and 5%).

Conclusion: The application of the uncertainty profile approach for full validation of a SPE-LC-MS/MS assay for the quantification of carbendazim has been successfully achieved.

Highlights: Implementation of a full validation strategy based on validation and measurement uncertainty with no additional effort using data from analytical validation under intermediate precision conditions at each level of concentration for carbendazim quantification in drinking water using SPE-LC-MS/MS. So we have shown the flexibility of this approach for carbendazim assay by LC-MS/MS. Indeed, It provides an efficient decision-making tool that allows selection and modification of β-content and γ-confidence values.