Fully automated platform for TDM analysis in serum samples

Significance of the Topic

Therapeutic drug monitoring (TDM) ensures safe and effective dosing for drugs with narrow therapeutic windows, such as antiepileptics, benzodiazepines, neuroleptics and tricyclic antidepressants. Achieving high throughput and reproducibility in clinical laboratories is critical for patient care, reducing toxicity, and guiding personalized treatments.

Aims and Overview of the Study

This study demonstrates a fully automated workflow to quantify key psychoactive drug classes in human serum. It aims to integrate sample preparation and LC-MS/MS analysis on a single platform for random-access operation, increasing throughput while maintaining analytical quality.

Methodology and Instrumentation

The platform combines a CLAM-2000 automated sample preparation unit with a Shimadzu Nexera X2 HPLC and LCMS-8060 triple quadrupole mass spectrometer. Disposable microvials or primary tubes are loaded at 8 °C. The CLAM-2000 performs protein precipitation by adding methanol and internal standard mix, shaking, incubating and 0.45 µm filtration. Processed extracts are delivered directly to the LCMS system. Chromatographic separation uses a Recipe MS9030 column with a binary gradient (mobile phases MS9007 and MS9008) and method-specific flow programs. Detection relies on optimized multiple reaction monitoring (MRM) transitions and internal standard calibration.

Main Results and Discussion

Calibration curves spanned low to high clinical concentration ranges for each drug panel, showing linear responses and accuracy between 85 % and 115 %. Intra-day and inter-day precision, assessed over four days and multiple replicates, yielded coefficients of variation within acceptable limits for clinical assays. Representative chromatograms at the lower limit of quantification confirmed selectivity and sensitivity. The random-access mode processed up to 91 analytes across four panels without manual intervention.

Benefits and Practical Applications

• Elimination of manual liquid handling reduces operator bias and improves traceability.
• Automation enhances reproducibility, lowers reagent consumption and operational costs.
• Random-access capability allows priority sample inclusion and flexible panel scheduling.
• Multiplexed LC-MS/MS quantitation supports comprehensive TDM in routine clinical labs.

Future Trends and Possibilities

Integration with high-resolution mass spectrometry, expansion to additional drug classes or biomarkers, and incorporation of artificial intelligence for data evaluation may further streamline workflows. Connectivity with laboratory information systems could enable real-time decision support and remote monitoring.

Conclusion

The fully automated CLAM-2000/Nexera X2–LCMS-8060 platform delivers robust, high-throughput TDM for multiple psychoactive drug classes in serum. It combines precision, flexibility and cost efficiency, making it well-suited for clinical and research laboratories.

References

• Ghilardi C, Vecchietti D, Kern K, Moreau S, Cabruja I. Fully automated platform for TDM analysis in serum samples. MSACL 2017.