Rapid analysis of drugs in plasma using probe electrospray ionization mass spectrometry

Importance of the Topic

Therapeutic drug monitoring of compounds with low effective concentrations such as immunosuppressants demands rapid and accurate plasma analysis. Conventional liquid chromatography–tandem mass spectrometry (LC-MS/MS) workflows require extensive sample cleanup and column maintenance to avoid matrix effects, delaying clinical decision-making. Probe electrospray ionization mass spectrometry (PESI-MS) directly ionizes samples with minimal pretreatment, offering potential for high-throughput quantitation in complex biological matrices.

Objectives and Study Overview

This study aimed to develop and validate a PESI-MS/MS method for the simultaneous quantitation of everolimus and abiraterone in plasma. It evaluated a simplified pretreatment consisting only of protein precipitation, optimized MS parameters for each drug, and assessed analytical performance over clinically relevant concentration ranges.

Methodology and Instrumentation

Sample Preparation:

• Commercial pooled plasma spiked with known amounts of everolimus and abiraterone.
• Protein removal via 1:1 dilution with ethanol, vortex mixing (10 s), and centrifugation at 10 000 × g for 5 min.
• 10 μL supernatant loaded onto PESI plate for direct analysis.

Instrumental Setup:

• PESI ion source (DPiMS-8060, Shimadzu).
• Triple quadrupole MS/MS (LCMS-8060, Shimadzu) in positive-ion MRM mode.
• MRM transitions: abiraterone m/z 350→156 (quantifier) and 170 (qualifier); everolimus [M+Na]+ m/z 980.8→389.3.

Main Results and Discussion

Calibration and Precision:

• Everolimus: linear response from 3–100 ng/mL (R2 = 0.997; %RSD ≤ 20%).
• Abiraterone: linear response from 2–400 ng/mL (R2 = 0.986; %RSD ≤ 30%).

Analysis Time:

• Total turnaround per sample: ~ 10 min including pretreatment.

The PESI technique showed minimal matrix suppression, eliminating the need for chromatographic separation and preserving column life.

Benefits and Practical Applications

PESI-MS/MS enables rapid, high-throughput quantification of low-concentration drugs in plasma with straightforward sample preparation. This approach can facilitate timely therapeutic drug monitoring in clinical and research laboratories without extensive chromatography.

Future Trends and Potential Applications

Integration of PESI with high-resolution MS could broaden the scope to metabolite profiling. Automation of the PESI workflow may further increase throughput for large-scale pharmacokinetic studies. Expansion to other drug classes and biological matrices will enhance its utility in precision medicine.

Conclusion

This work demonstrates that PESI-MS/MS provides a robust, fast, and simple alternative to traditional LC-MS/MS for everolimus and abiraterone quantification in plasma, delivering reliable results within 10 minutes.

References

No additional references were cited.