Validation of analytical methods based on mass spectrometric detection according to the "2002/657/EC" European decision: guideline and application

The purpose of the present paper is to present an interpretation of the concepts introduced in the new 2002/657/EC European decision and to propose a practical guideline dedicated to the validation of analytical methods based on mass spectrometry. Considering both the statistical significance of the results and practical aspects, the minimal number of assays permitting a satisfying validation to be achieved appeared to be 45 for qualitative methods and 55 for quantitative methods. The parameters validated with this protocol are specificity, sensitivity, linearity, decision limit (CCalpha), repeatability, detection capability (CCbeta) and recovery. It is proposed to estimate these parameters on the basis of the most intense (or unique) ion for screening methods and on the basis of the "critical ion" (less intense ion permitting the unambiguous identification of the analyte according to the required number of identification points) for confirmatory methods. An application of this guideline is presented and discussed, through the validation of a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method dedicated to the determination of the corticosteroid triamcinolone acetonide (Tri Acn) in meat samples. (C) 2002 Elsevier Science B.V. All rights reserved.