Shimadzu Journal Vol. 09 - Clinical Research

Importance of the Topic

A growing need exists for faster, more accurate and minimally invasive analytical methods to support clinical research, diagnostics and quality control in analytical chemistry. Recent advances in plasmonic nanostructures, ambient ionization techniques and chromatographic–mass spectrometric workflows promise to transform disease detection, sample quality assessment and drug monitoring.

Objectives and Overview of the Articles

• Assess the stability of silver nanorods under aqueous conditions to guide plasmonic sensor design.
• Demonstrate a rapid, ambient Probe Electrospray Ionization (PESI)–MS method for routine blood sample quality evaluation.
• Develop HPLC and LC–MS/MS assays for quantifying COVID-19 therapeutic drugs (remdesivir, GS-441524, favipiravir) in human plasma.

Used Methodology and Instrumentation

• Silver nanorods grown by glancing-angle physical vapor deposition characterized by SEM, UV-Vis, AFM/Kelvin-probe SPM and Raman spectroscopy.
• Blood QC: 2 µL plasma extraction, 1:20 MeOH/DMSO precipitation, PESI-MS on Shimadzu DPiMS-2020, dual-mode ionization, data binned and machine-learning classification.
• Remdesivir/GS-441524: simultaneous quantitation in plasma by automated LC–MS/MS with online sample preparation.
• Favipiravir: both automated LC–MS/MS and HPLC–fluorescence assays developed for rapid clinical monitoring.
• Instrumentation: Shimadzu DPiMS-2020 PESI-MS, UV-3600 UV-Vis, SPM-9700 HT, LCMS-8060/9030, HPLC systems.

Main Results and Discussion

• Silver Nanorod Corrosion: Ag nanorods rapidly oxidize and coarsen within hours in non-degassed water, degrading plasmonic optical response; degassed water preserves morphology over days.
• Blood QC via PESI-MS: 1-hour ambient QTOF spectra from 2 µL plasma yielded ~1 200 features; 18 key metabolite ions discriminated a 3 h processing delay with ROC AUC > 0.95 across multiple classifiers.
• Remdesivir Analysis: Automated LC-MS/MS method achieved simultaneous detection of remdesivir and its active metabolite GS-441524 with robust precision suitable for clinical pharmacokinetics.
• Favipiravir Quantitation: Both LC-MS/MS and conventional HPLC–fluorescence methods deliver sub-µg/mL sensitivity in plasma, enabling therapeutic drug monitoring in COVID-19 patients.

Benefits and Practical Application of the Methods

• Improved sensor reliability by understanding nanostructure corrosion under real-world conditions.
• High-throughput blood sample QC requiring minimal training, small plasma volumes and rapid turnaround, reducing preanalytics errors.
• Clinically deployable LC–MS/MS assays for emerging COVID-19 therapies, supporting dosing optimization and drug–drug interaction studies.

Future Trends and Potential Applications

• Integration of plasmonic sensors into portable point-of-care devices with long-term stability.
• Fully automated, ambient MS platforms for sample quality control across biobanking, clinical trials and diagnostics.
• Expansion of multiplex LC–MS/MS panels for pharmacokinetic and biomarker analysis in infectious diseases and personalized medicine.

Conclusion

Combined advances in nanostructure characterization, ambient ionization MS and automated chromatographic MS/MS demonstrate the feasibility of rapid, robust and miniaturized analytical solutions for clinical research and diagnostics. Understanding real-world sample and sensor behavior, coupled with machine learning for data interpretation, will drive the next generation of personalized testing and quality-assured analytics.

Reference

• Stagon, S. et al. Rapid corrosion of silver nanorods in water: Implications for plasmonic sensing. Anal. Chem. 2021.
• Bordag, N. et al. PESI metabolomics for blood sample quality evaluation. medRxiv 2021.
• Kawakami, D. et al. HPLC and LC–MS/MS methods for remdesivir and favipiravir in plasma. Shimadzu App. Note 2021.