Bioanalytical LC-MS/MS validation of therapeutic drug monitoring assays in oncology

Area of Science:

• Clinical Chemistry
• Pharmacology
• Bioanalytical Science

Background:

• Therapeutic drug monitoring (TDM) is crucial for optimizing drug efficacy and safety across various therapeutic areas, including oncology.
• The increasing demand for TDM necessitates the development and validation of new analytical assays.
• Existing bioanalytical validation guidelines (e.g., FDA, EMA) are stringent but may not be fully applicable to TDM assays due to their intended use.

Purpose of the Study:

• To review and evaluate current practices in the method validation of assays specifically designed for TDM.
• To provide recommendations for future validation strategies of TDM assays.
• To ensure the reliability and accuracy of TDM results for clinical decision-making.

Main Methods:

• Systematic literature review of publications detailing method validation for TDM assays.
• Analysis of validation approaches described in the reviewed literature.
• Comparison of current TDM assay validation practices against established bioanalytical guidelines.

Main Results:

• A significant variation in validation approaches for TDM assays was observed across studies.
• Many TDM assays are validated using limited approaches, often tailored to their specific clinical application.
• Current practices sometimes deviate from, or do not fully implement, standard bioanalytical validation requirements.

Conclusions:

• A tailored, risk-based validation strategy is appropriate for TDM assays, considering their intended use.
• Clearer guidelines or recommendations are needed to standardize TDM assay validation.
• Implementing robust yet appropriate validation ensures the clinical utility and reliability of TDM.