The Agilent StreamSelect LC/MS Solution: Increasing the Throughput of a Triple Quadrupole Mass Spectrometer

Significance of the Topic

The demand for high-throughput quantitative analysis in biological, pharmaceutical, and clinical laboratories continues to grow. Conventional single-stream LC/MS/MS workflows often leave the mass spectrometer idle during segments of a chromatographic run when no target analytes are eluting. Maximizing instrument utilization without sacrificing sensitivity, reproducibility, or ease of use is therefore critical for improving lab productivity and lowering operational costs.

Goals and Study Overview

This overview evaluates the Agilent StreamSelect LC/MS solution designed to double sample throughput by operating two parallel HPLC streams with a single triple quadrupole mass spectrometer. Key objectives include demonstrating how innovative hardware integration and software control can:

• Eliminate idle time in MS detection
• Maintain quantitative performance equivalent to traditional systems
• Enable seamless method transfer and simple batch management

Methodology and Instrumentation

The StreamSelect configuration comprises two complete LC subsystems—each with binary/quaternary pumps, thermostatted column compartments, injection modules, and a stream selection valve—feeding one Agilent 6400 Series triple quadrupole mass spectrometer. An optional online sample cleanup variant adds trapping columns and switching valves upstream of each analytical column to remove salts and matrix in parallel. Chromatographic streams are staggered so that only one effluent at a time is routed to the MS, orchestrated by MassHunter StreamSelect software.

The software workflow uses a single LC/MS method for both streams. A Profile Editor captures retention windows and instrument timing into reusable templates. Batch lists in common formats (.csv, .txt, .xls, .xlsx) are submitted in three clicks. A Calibrator Map feature assigns plate positions for calibrators, blanks, QCs, and unknowns, and can insert system verification samples at defined intervals.

Results and Discussion

Quantitative comparisons for 25-hydroxy vitamin D2 and D3 across both LC streams yielded linear calibration (R² > 0.999) with statistically equivalent slopes and intercepts. Retention time and peak area reproducibility for clozapine analyses over 22 injections showed less than 0.5% variation between streams. In case of LC pump failure or overpressure, the software automatically redirects all subsequent samples to the functional stream without data loss or mislabeling.

Benefits and Practical Applications

• Up to 2× throughput without additional mass spectrometer investment
• Fast adoption of existing LC/MS methods—no revalidation required
• Robust error recovery and dynamic batch execution reduce rework
• Optional online cleanup accelerates sample preparation and protects MS from contamination

This solution suits clinical pharmacokinetics, routine biomarker assays, environmental monitoring, and high-volume QA/QC workflows.

Future Trends and Opportunities

Further integration with automated sample handling and expanded multiplexing of more than two streams could push throughput even higher. Incorporating machine-learning algorithms for retention time prediction and adaptive scheduling may streamline method development. Coupling StreamSelect with emerging high-resolution mass spectrometers could broaden applicability to non-targeted screening and metabolomics.

Conclusion

The Agilent StreamSelect LC/MS solution effectively doubles sample throughput while preserving analytical performance and user-friendliness. Its software-driven orchestration, robust error handling, and flexible instrument configurations make it a practical upgrade for labs requiring high productivity without compromising data quality.

References

Agilent Technologies Inc. The Agilent StreamSelect LC/MS Solution: Technical Overview. Published October 2013. 5991-3274EN.