Automating Sample Preparation for LCMS with Shimadzu’s CLAM-2000 SERIES

Importance of the Topic

Automating sample preparation for LC-MS/MS workflows in forensic laboratories addresses critical challenges of labor intensity, lengthy turnaround times, and variability. By integrating pretreatment with analysis, laboratories can improve throughput, reproducibility, and data quality for complex biological samples such as blood, urine, tissues, and oral fluids.

Objectives and Study Overview

This work presents Shimadzu’s CLAM-2000 series, the first fully integrated automated platform for LC-MS/MS workflows. The performance of the system was evaluated in three forensic applications: drug screening in oral fluid, multi-tissue drug quantitation, and illicit drug analysis in urine.

Methodology and Instrumentation

• Automated workflow: Internal standard and solvent dispensing, mixing, shaking, filtration, and direct transfer to the LC autosampler.
• Oral fluid method: Quantisal swab extraction, 10–60% methanol gradient in 7 min, analysis of 122 drugs with deuterated standards; first-cycle time 11 min, subsequent cycles 7 min.
• Multi-tissue method: Analysis of 15 target analytes and 4 internal standards in whole blood, liver, brain, spleen, and muscle; calibration 10–1000 ng/mL with five-point curves.
• Urine screening: Protein crash with ACN/MeOH, analysis of 18 illicit drugs and 14 isotope-labeled standards; calibration 20–200 ng/mL; MRM monitoring for quantitation.

Used Instrumentation

• Shimadzu CLAM-2000 series automated sample preparation module
• Shimadzu Nexera LC system
• Shimadzu LCMS-8050 triple quadrupole mass spectrometer

Key Results and Discussion

• Oral fluid analysis achieved relative standard deviations ≤ 10% for all 122 compounds, demonstrating high reproducibility under fully automated conditions.
• Multi-tissue quantitation showed linear responses (R² > 0.99) for all compounds across different matrices, confirming robustness of the workflow.
• Urine analysis delivered accuracy within ±20% for most drugs (except methadone at low level), R² > 0.995, and process efficiency of 62–122%, indicating reliable quantitation and high specificity.
• Sample preparation time was reduced from over 60 minutes using traditional methods to approximately 6 minutes per sample, aligning with LC-MS run times and maximizing laboratory throughput.

Benefits and Practical Applications

• Eliminates manual handling steps to minimize human error and cross-contamination.
• Parallel processing of up to 60 samples increases throughput and matches LC-MS/MS cycle times.
• Reduces labor costs and frees analysts for higher-value tasks in forensic and clinical laboratories.
• Applicable to a wide range of biological matrices for comprehensive forensic investigations.

Future Trends and Opportunities

• Integration with advanced software for real-time data evaluation and quality assurance.
• Expansion of automated workflows to include on-module derivatization and solid-phase extraction.
• Development of multiplex assays for emerging contaminants and novel psychoactive substances.
• Adaptation to high-throughput clinical diagnostics, therapeutic drug monitoring, and environmental screening.

Conclusion

Shimadzu’s CLAM-2000 series represents a major advancement in forensic LC-MS/MS workflows by delivering fully automated sample preparation seamlessly integrated with analysis. This solution drastically reduces preparation times, enhances reproducibility, and ensures high-quality data across diverse matrices, meeting the stringent demands of modern forensic laboratories.

Reference

No literature references were provided in the source material.