Rapid MALDI-MS Assays for Drug Quantification in Biological Matrices: Lessons Learned, New Developments, and Future...

Area of Science:

• Analytical Chemistry
• Biotechnology
• Pharmacology

Background:

• Therapeutic drug monitoring (TDM) traditionally relies on methods with limitations in sensitivity and specificity.
• Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) offers potential for TDM but faces challenges in matrix selection and ionization processes.

Purpose of the Study:

• To review the essential developments for establishing MALDI-MS assays for drug quantification in biological matrices.
• To outline parameters for regulatory-compliant bioanalytical method validation using MALDI-MS.
• To identify current challenges and future perspectives for MALDI-MS in TDM.

Main Methods:

• Review of existing literature and case studies on MALDI-MS applications in drug quantification.
• Analysis of critical parameters including matrix suitability, crystallization properties, and MS instrumentation.
• Discussion of regulatory guidelines for bioanalytical method validation.

Main Results:

• Successful development of MALDI-MS assays requires careful consideration of matrix-analyte interactions and crystallization properties.
• Optimization of MS instrumentation is crucial for sensitive detection of low drug concentrations.
• Concrete examples illustrate the steps and challenges in validating MALDI-MS methods for tissue and plasma samples.

Conclusions:

• MALDI-MS can be a powerful technique for therapeutic drug monitoring when key development parameters are controlled.
• Addressing current challenges in matrix selection and automation is necessary for broader adoption.
• Further research and standardization are needed to establish MALDI-MS as a universal TDM method.