A Comparative Analysis of Analytical Validation Approaches for Quality Assurance: Exploring Holistic Strategies in the Validation of Quantitative Methods-A Case Study of Hesperidin.

Abstract

Background: Analytical validation is a sequence of operations aiming to evaluate the accuracy, reliability, and cost of analytical results for making informed decisions in method selection and meeting the requirements of regulatory institutions.

Objective: This study aims to perform an analytical validation by comparing three different approaches: the accuracy profile, the uncertainty profile, and the conventional validation to assess the capability of each method in confirming the robustness of the results.

Methods: The accuracy profile offers a comprehensive assessment of analytical performance and integrates systematic and random errors to determine if future results will satisfy the predefined acceptance limits. Meanwhile, the uncertainty profile, which is complementary and innovative, allows the uncertainty estimation from validation data. These approaches were developed after conventional validation that relies on statistical methodologies based on separate evaluations of method criteria to provide a comparative framework for evaluating new methods.

Results: This comparison will give recommendations for best practices related to analytical validation. The uncertainty profile is a graphical decision-making tool for determining full validation by integrating analytical validation and the estimation of measurement uncertainty, evaluating two statistical methods: β-expectation tolerance intervals and β-content, γ-confidence tolerance intervals, using a formula introduced by Saffaj δ Ihssane, predicting that 95% of future results will fall within the acceptance limits of ± 5%, revealing that the tolerance intervals for β-expectation are smaller than β-content, γ-confidence.

Conclusion: The total error approaches offer robust recommendations for optimal methods for routine application.

Highlights: This study highlights the critical need for appropriate analytical validation and the challenges arising from the absence of clear guidelines for that purpose. Different approaches emphasize the significant impact of the choice of an adequate method, which remains pivotal for providing accurate results under real-world scenarios. Concrete examples and simulations illustrate the viewpoints associated with different approaches to making decisions.