A STATISTICAL APPROACH BASED ON THE TOTAL ERROR CONCEPT FOR VALIDATION THE BIOANALYTICAL METHOD: APPLICATION TO THE SPECTROPHOTOMETRIC DETERMINATION OF TRACES AMOUNT OF ACETAMINOPHEN IN HUMAN PLASMA

Abstract

Objective: The use of the classical approach of analytical validation, in practice or in the literature, is common. However, statistical verification, that looks separately the two errors (such as bias and precision) to make a decision, presents a risk to declare that an analytical method is valid while it is not, or conversely. To minimize this risk, a new approach based on the concept of total error was proposed. Methods: This approach proposes a calculation the two sided tolerance interval by combining the two errors; bias and precision, in order to examine the validity of an analytical and bioanalytical method at each concentration level. In this paper, we aim to demonstrate the applicability and simplicity of the both methods based on the total error approach: accuracy profile and uncertainty profile. This study will be illustrated by validation case of a spectrophotometric method for the determination of trace amounts of acetaminophen in human plasma. Results: After the introduction of the correction coefficient which is worth 1.16, the results obtained with accuracy profile approach show clearly that the bioanalytical method is valid over a concentrations range of [100.34- 500] µg mL-1 since the upper and lower 90%-expectation tolerance limits have fallen within the two acceptance limits of ± 20%. The same results found using the uncertainty profile approach because the "two - sided 66.7%-content, 90% -confidence tolerance intervals "are found within two acceptance limits of ± 20% over the range of [170; 500] µm mL-1. Conclusion: The excellence of the total error approach was showen since it enables successfully to validate the analytical procedure as well the calculation of the measurement uncertainty at each concentration level