An overall validation approach based on β-content, γ-confidence tolerance interval and uncertainty profile: Application for LC-MS/MS quantification of Carbendazim in drinking water.

Abstract

The Carbendazim is a fungicide which can seep into the water supply, presenting a public health risk, therefore the accurate trace determination of this substance is very important. The purpose of the study is to perform 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. Quantification of Carbendazim using solid-phase extraction coupled with LC/MS-MS in order to ensure the accuracy of the analytical method and to master the risk of its routine application. An overall validation methodology based on two side tolerance interval type β-content, γ-confidence has been applied for the validation and estimation of uncertainty by building a decision graphical tool called "uncertainty profile" by using the statistical process known as the "Satterthwaite approximation" with no recourse to supplementary data by satisfying intermediate precision condition for each concentration level within the acceptance limits fixed in advance. As a result, the process of the 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 β γ-CCTI fell inside acceptable limits of ± 10%, and the relative expanded uncertainty didn't surpass 7% regardless of the β values (66.7%, 80%, 90%) and the 1- γ=risk (10%, 5%). 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.