Investigations beyond standard operating procedure on internal standard response

Area of Science:

• Bioanalytical Chemistry
• Pharmacokinetics
• Drug Development

Background:

• Internal standard (IS) response monitoring is standard practice in regulated bioanalytical studies to manage sample outliers.
• Current practices often focus on individual sample acceptance/rejection, potentially overlooking broader systemic issues.

Purpose of the Study:

• To highlight the importance of investigating internal standard response trends and systemic differences.
• To emphasize that atypical IS response can indicate underlying bioanalytical method problems.

Main Methods:

• Routine monitoring of internal standard response during analytical runs.
• Evaluation of trends in IS response across samples.
• Comparison of IS response between spiked and incurred samples.
• Formal investigation procedures for atypical results.

Main Results:

• Individual sample outlier management is insufficient for detecting systemic method issues.
• Atypical internal standard response patterns can signal problems with the bioanalytical method.
• Systemic differences between spiked and incurred samples warrant investigation.

Conclusions:

• Investigating internal standard response trends and systemic variations is essential for robust bioanalytical data.
• Modifications to bioanalytical methods may be necessary to ensure a stable internal standard response.
• Comprehensive investigations, beyond simple sample rejection, are critical for method validation and regulatory compliance.