Agilent 6490 Triple Quadrupole LC/MS System

Significance of the Topic

The accurate quantitation of trace compounds in complex matrices underpins advances in pharmaceuticals, clinical research, food safety, forensic toxicology, and environmental analysis. Ultra-sensitive detection extends the ability to monitor low-abundance analytes, enabling faster method development, simplified sample preparation, and greater confidence in results.

Objectives and Study Overview

This application note presents the Agilent 6490 Triple Quadrupole LC/MS system with iFunnel technology. Key goals include achieving zeptomole-level sensitivity at conventional flow rates, widening linear dynamic range, and maintaining high throughput and reliability for demanding quantitative analyses.

Methodology and Instrumentation

The Agilent 6490 combines three core innovations:

• Agilent Jet Stream electrospray focusing and desolvation to generate concentrated ion beams.
• Hexabore sampling capillary with six parallel channels to increase ion transmission.
• Dual-stage ion funnel design to maximize ion transfer into the first quadrupole while reducing neutral and solvent loads.

High-frequency quadrupole electronics support fast scan rates and compatibility with rapid UPLC separations. Automated multi-analyte tuning and 96-well plate autosampling further streamline workflows.

Main Results and Discussion

The system delivers detection limits down to 100 zeptomoles on-column, with linear response over six orders of magnitude (R2 ≈ 0.997). Continuous operation of 2,000 injections of low-level analytes in plasma exhibited RSD <6% for peak areas. Key demonstrations include:

• 2.5 fg fluticasone propionate in diluted plasma without SPE/LLE.
• 1–28 amol peptide quantitation on a standard 2 mm column.
• Estradiol detection at 10 pg/mL in human plasma with 10 µL injection.
• Simultaneous quantitation and confirmation of 300 pesticides in complex tea matrices at ≤0.25% of MRL.

Benefits and Practical Applications

The enhanced sensitivity and expanded dynamic range allow “dilute-and-shoot” sample prep, minimizing labor and consumable costs. High throughput automation and robust performance support large sample sets with minimal downtime. Broad application scope spans drug metabolism studies, biomarker discovery, food safety screening, and environmental monitoring.

Future Trends and Potential Applications

Emerging trends include integration with ion mobility for enhanced separation, miniaturized flow and microfluidic interfaces for single-cell analyses, and AI-driven method optimization. Continued improvements in funnel design and data acquisition modes are expected to further lower detection limits and accelerate workflows.

Conclusion

Agilent’s 6490 Triple Quadrupole LC/MS with iFunnel technology sets a new standard for quantitative mass spectrometry by combining unprecedented sensitivity, broad dynamic range, and high throughput in a compact benchtop format. It addresses the most challenging trace-level assays while maintaining ease-of-use and reliability.

Used Instrumentation

• Agilent 6490 Triple Quadrupole LC/MS system
• iFunnel ion sampling assembly
• Agilent Jet Stream ESI source
• Hexabore sampling capillary
• Agilent 1200/1290 Infinity Series LC and autosampler