LC walk-up system using the Agilent 1200 Series LC Method Development Solution and Agilent Easy Access software

Importance of the Topic

Walk-up LC/MS platforms address the growing demand for rapid, in-time analytical feedback in synthetic chemistry laboratories. By combining liquid chromatography with mass spectrometry and automated sample handling, these systems empower chemists to monitor reaction progress, scout columns for preparative cleanup, and verify compound purity without reliance on a dedicated analytical team.

Objectives and Study Overview

This application note describes the implementation of an Agilent 1200 Series LC Method Development Solution paired with Agilent Easy Access software and a 6410 single quadrupole MS. The goals were to:

• Enable multiple user groups to perform reaction monitoring, column scouting, and purity checks on a single LC/MS platform
• Provide access to up to eight columns of varied selectivity and dimensions
• Implement priority scheduling and automated reporting

Methodology and Instrumentation

The system configuration was managed by a superuser who defined projects, user permissions, chromatographic methods, and column setups via Easy Access. Key instrumentation included:

• Agilent 1200 Series binary pump SL with degasser
• Agilent 1200 Series high-performance autosampler SL Plus
• Two thermostatted column compartments SL Plus with valve drives (up to eight columns per cluster)
• Method development valve kit (G4230B) for high pressure, low dispersion flow paths
• Agilent 1200 Series diode array detector (DAD) SL
• Agilent 6410 single quadrupole MS with multimode source
• ZORBAX RRHT columns (50×2.1 mm, 100×2.1 mm, 150×2.1 mm; 1.8 µm particles)
• Agilent ChemStation B04.01 with Easy Access software

Main Results and Discussion

Column scouting experiments with four 50×2.1 mm RRHT phases identified ZORBAX SB-C18 as optimal for preparative cleanup, later scaled to a 150 × 21.2 mm prep column. Purity checks post-fractionation confirmed sample integrity and absence of thermal degradation. Reaction monitoring using a fast-kinetics method revealed complete conversion to the desired product within 1.5 h, with MS scan data characterizing two side products for further study. In a third use case, LC/MS analysis of a slow reaction highlighted suboptimal yields and informed adjustments to reaction parameters.

Benefits and Practical Applications

The walk-up LC/MS approach enhances chemist productivity by delivering automated:

• Access control for multiple user groups
• Priority-based sample scheduling
• Instant e-mail reporting of results
• Flexible column switching and method selection

Such a system streamlines workflows in drug discovery, process development, and QA/QC labs.

Future Trends and Potential Applications

Further integration of artificial intelligence for automated method optimization and peak identification will expand the capabilities of walk-up systems. Increased multiplexing of detectors (MS/MS, high-resolution MS) and remote access portals promise even faster decision cycles in synthetic and analytical chemistry. The adoption of more robust, high-temperature columns and greener solvents will support sustainable development goals.

Conclusion

The Agilent 1200 Series LC Method Development Solution with Easy Access software and a 6410 MS delivers a versatile, walk-up LC/MS environment. It meets diverse analytical demands—reaction monitoring, column scouting, and purity analysis—while optimizing user throughput and data reporting.

References

1. A.G. Huesgen, Agilent 1200 Series LC method development solution – Automated method development with up to eight columns. Agilent Technical Note 5989-9338EN, 2008
2. W. Duncan, D. McIntyre, Increasing productivity with LC/MS Easy Access software. Agilent Technical Note 5988-5525EN, 2002
3. D. McIntyre, Continuous Operation of a High Throughput LC/MS System in a Walk Up Environment. Agilent Technical Note 5989-6714EN, 2007