Evaluation of LC-MS Data under Ultra-High Throughput Conditions

Significance of the Topic

Ultra-high-throughput liquid chromatography–mass spectrometry (LC-MS) is critical for accelerating compound analysis in pharmaceutical, environmental, and industrial laboratories. By minimizing injection and cycle times, laboratories can process larger sample sets rapidly, reducing time to result and improving productivity without sacrificing sensitivity or reproducibility.

Objectives and Study Overview

The study aimed to evaluate the performance of a novel high-speed autosampler and LC-MS/MS system under ultra-high-throughput conditions. Key goals included assessing injection speed, cycle time, carryover, and reproducibility when performing up to four analyses per minute.

Methodology and Instrumentation

The analytical setup combined:

• Shimadzu Nexera UHPLC system with SIL-30ACMP autosampler featuring a 7-second injection time and 14-second cycle time
• CTO-30AS column oven enabling flexible plate types and minimized dead volume
• Shimadzu LCMS-8030 triple quadrupole mass spectrometer with 15 000 u/sec scan speed and 15 msec polarity switching

Multi-rinse protocols using up to four solvents were implemented to minimize carryover between injections.

Main Results and Discussion

The combined system achieved four analytical runs per minute without load-ahead or pre-injection steps. Key findings included:

• Consistent injection-to-injection reproducibility (1.0% RSD at 0.5 µL)
• Extremely low carryover (0.0001% for chlorhexidine at 500 µg/mL)
• High scan throughput maintained during rapid polarity switching, supporting both LC/MS and LC/MS/MS workflows
• Capacity to process 2304 samples per batch using mixed 96/384-well plates and 1.5 mL vial racks

Benefits and Practical Applications

• Enhanced laboratory productivity through the world’s fastest reported LC-MS cycle time (14 sec)
• Reduced sample carryover supporting high-sensitivity quantitation in pharmacokinetic and drug discovery studies
• Flexible sample handling with open-access rack design and compatibility with multiple plate formats
• Potential integration with third-party mass spectrometers to extend front-end capabilities

Future Trends and Opportunities

Advances in automation, multiplexed injection strategies, and software-driven method optimization are expected to further elevate throughput and data quality. Integration with high-resolution and ion mobility mass spectrometry may expand applications in metabolomics, proteomics, and environmental screening. Continuous innovation in microfluidics and miniaturized LC systems will drive deeper analysis at reduced solvent consumption.

Conclusion

This evaluation demonstrates that ultra-high-throughput LC-MS with rapid injection and robust autosampler design delivers exceptional speed, reproducibility, and minimal carryover. The approach meets the demanding requirements of modern analytical workflows, offering a scalable solution for high-sample-volume environments.