Using the DPiMS-8060 Mass Spectrometer to Analyze Drugs in Plasma (1) - A Quantitative Analysis of Everolimu

Importance of the Topic

Quantitative measurement of drug concentrations in plasma is essential for pharmacokinetic research, therapeutic monitoring, and drug development. Traditional LC/MS methods require extensive deproteinization and column maintenance, extending analysis time and risking matrix-related contamination.

Study Objectives and Overview

The aim was to evaluate the DPiMS-8060 probe electrospray ionization (PESI) system coupled to an LCMS-8045 mass spectrometer for rapid, reliable quantification of everolimus in plasma with minimal sample preparation.

Methodology and Instrumentation

Samples were deproteinized by adding equal volumes of LC/MS-grade ethanol to plasma, vortexed, centrifuged, and the supernatant directly analyzed. Ten microliters of supernatant were introduced via the PESI probe, eliminating the need for an LC column. Analysis time per sample, including pretreatment, was approximately 10 minutes.

• Instrumentation Used: LCMS-8045 with DPiMS-8060 PESI unit in positive ESI mode.
• Mass Spectrometer Settings: Precursor ion m/z 980.8 ([M+Na]+), product ion m/z 389.3, collision energy -51.0, MRM mode for quantitation, Q3 scan for profiling. Source and actuation parameters were set as per Tables 1 and 2.

Main Results and Discussion

Everolimus formed three adduct ions, with [M+Na]+ selected for quantification. Fragmentation yielded a dominant ion at m/z 389.3. Calibration showed excellent linearity from 3 to 50 ng/mL (R2=0.9972). Intra-assay precision (%RSD) remained below 20% across the range. The method demonstrated minimal matrix interference and no column-related variability.

Benefits and Practical Applications

• Fast throughput suitable for therapeutic drug monitoring and pharmacokinetic studies.
• Reduced maintenance and no column degradation due to direct ionization.
• Simple sample preparation minimizes matrix effects and instrument contamination.
• Applicable to high-throughput clinical and research laboratories.

Future Trends and Applications

Advancements may include automated sample handling, application to additional drug classes, integration with high-resolution MS, and real-time patient monitoring. The PESI approach could expand to biotherapeutic analysis and on-site clinical testing.

Conclusion

The DPiMS-8060 PESI method provides a rapid, robust, and precise platform for quantifying everolimus in plasma, offering significant workflow improvements over conventional LC/MS. Its minimal sample prep and high reproducibility support broader adoption in clinical and industrial settings.