Quimica

128

Grasas y Aceites Vol. 53. Fasc. 1 (2002), 128-143

Validation of Analytical Methods
By Ricard Boqué, Alicia Maroto, Jordi Riu and F. Xavier Rius* Department of Analytical Chemistry and Organic Chemistry University Rovira i Virgili Pl. Imperial Tàrraco, 1, 43005-Tarragona, Spain
CONTENTS
1. 2. 3. Introduction Validation and fitness-for-purpose Analytical requirements and performancecriteria 3.1. Trueness 3.1.1. Certified reference materials (CRM), reference materials and in-house materials. 3.1.2. Reference methods. 3.1.3. Proficiency testing 3.1.4. Spiked samples 3.1.5. Assessment of trueness in restricted concentration ranges 3.1.6. Assessment of trueness in large concentration ranges. Recovery studies 3.2. Precision and uncertainty 3.2.1. Calculation of thewithin-laboratory precision 3.2.2. Calculation of the repeatability limit 3.2.3. Calculation of the "internal reproducibility" limit 3.3. Uncertainty 3.3.1. Uncertainty of the assessment of trueness, utrueness 3.3.2. Uncertainty of sample pretreatments, upretreatments 3.3.3. Uncertainty of other terms 3.4. Linear and working ranges 3.5. Limit of detection (LOD) 3.5.1. Estimating the standard deviations of the netconcentrations 3.5.2. Alternatives for LOD calculation 3.6. Limit of quantification (LOQ) 3.7. Selectivity (specificity) 3.8. Sensitivity 3.9. Ruggedness (or robustness) The basic principles of method validation Performing the method validation Inter-laboratory comparison as a means for method validation In-house validation Reporting method validation References

SUMMARY Validation ofanalytical methods.
In this paper we shall discuss the concept of method validation, describe the various elements and explain its close relationship with fitness for purpose. Method validation is based on the assumption that a series of requirements are fulfilled and we shall explain how these requirements are selected, the way in which evidence is supplied and what work has to be carried out in thelaboratory. The basic principles of method validation and the different ways to validate a methodology, by inter-laboratory comparison or performing an in-house validation, are also described.

KEY-WORDS: Fitness-for-purpose - In-house validation Method validation - Performance criteria.

1. INTRODUCTION Analytical information can be used for a variety of purposes: to take decisions involving thecontrol of the manufacturing process of a product, to assess whether a product complies with regulatory limits, to take decisions about legal affairs, international trade, health problems or the environment. Consequently, the producer of analytical results must not only ensure that they are reliable but also that they have all the elements that give confidence to the user. Quantitative analyticalresults are expressed as “estimated value ± U” where “estimated value” is the estimate of the true value obtained when the analytical method is applied to the test sample. “U” represents the uncertainty associated to the estimated value. Nowadays, the users of test results are also interested in other characteristics. They also require, for example, that the estimated value be repeatable undercertain conditions, that the analytical method provide similar results when the experimental conditions are slightly modified and that the test method be capable of quantifying very low concentrations of the analyte. Since it is materially impossible to guarantee these characteristics for every single test result, the international analytical institutions have developed a system that ensures thequality of the results if they have been obtained under certain conditions. This quality assurance system, although highly developed nowadays, is in continuous evolution so that it can adapt to the new requirements of society.

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RESUMEN Validación de métodos analíticos.
En este artículo se discute el concepto de validación del método, se describen los elementos que la componen y...