Quantification of pharmaceutical compounds in tissue and plasma samples using selective ion accumulation with...

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Pharmaceutical Analysis

Background:

• Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) offers rapid analysis and imaging capabilities for pharmaceutical quantification.
• Traditional MALDI-MS faces limitations in dynamic range and detection limits due to chemical noise and lack of chromatographic separation.
• Internal standards are crucial for compensating variability in MALDI sampling.

Purpose of the Study:

• To develop and validate a novel MALDI-MS quantification workflow utilizing multiple sequential mass isolation windows.
• To improve the limit of detection, accuracy, and precision for pharmaceutical compounds in complex biological matrices.
• To demonstrate the applicability of the method for both biofluid and tissue imaging mass spectrometry.

Main Methods:

• A hybrid mass spectrometer equipped with a quadrupole mass filter (QMF) was employed.
• Multiple narrow mass isolation windows were sequentially applied using the QMF to fractionate ions.
• The workflow was tested for quantifying enalapril in human plasma and simultaneously quantifying enalapril, ramipril, and verapamil.
• The method was also applied to quantify enalapril in rat brain tissue using imaging mass spectrometry.

Main Results:

• The multiple mass isolation window approach significantly reduced the limit of detection for pharmaceutical quantification.
• Relative standard deviations were consistently below 10%, and accuracy remained above 85% for drug analysis in plasma.
• Quantification of enalapril in rat brain tissue using imaging mass spectrometry showed high agreement with LC-MS, achieving 104% accuracy.

Conclusions:

• The developed MALDI-MS workflow with multiple sequential mass isolation windows effectively mitigates chemical noise, enhancing quantification performance.
• This method provides a robust and sensitive alternative to traditional LC-MS for pharmaceutical analysis in complex samples, including tissue imaging.
• The improved accuracy and precision demonstrate the potential of this technique for various quantitative applications in drug development and analysis.