Incurred sample accuracy assessment: design of experiments based on standard addition

Area of Science:

• Analytical Chemistry
• Pharmacokinetics
• Bioanalysis

Background:

• Random and systematic analytical errors impact bioanalytical data quality and pharmacokinetic parameter precision/accuracy.
• Current Good Laboratory Practice (GLP) bioanalysis primarily addresses random errors through reanalysis of incurred samples.
• Systematic errors, affecting method trueness and data accuracy, are less attended in current GLP bioanalysis guidelines.

Purpose of the Study:

• To propose and illustrate a method for assessing systematic errors in GLP bioanalysis.
• To enhance the accuracy and trueness of pharmacokinetic parameters derived from bioanalytical data.
• To extend current GLP bioanalysis guidelines with a focus on systematic error evaluation.

Main Methods:

• Application of standard addition experiments to quantify relative systematic errors.
• Estimation of incurred sample accuracy using the standard addition approach.
• Illustration of the method using bioanalytical data from a bioequivalence study of alendronate.

Main Results:

• The standard addition method provides an estimate for incurred sample accuracy.
• The proposed approach can identify and quantify systematic errors in bioanalytical methods.
• The accuracy of bioanalytical results for alendronate was assessed using this novel approach.

Conclusions:

• Standard addition experiments are a valuable extension to current GLP bioanalysis guidelines for assessing systematic errors.
• Implementing this method can lead to more precise and accurate pharmacokinetic parameters.
• This approach contributes to improved data quality and reliability in drug development and bioequivalence studies.