Robustness of the Agilent Ultivo Triple Quadrupole LC/MS with Standard ESI Ion Source for High-Throughput Testing of Drugs in Serum

Importance of the topic

Forensic toxicology laboratories require analytical techniques capable of delivering high sensitivity, accuracy, and uninterrupted performance to process large sample batches over extended periods. Reliable quantification of drugs in serum is critical for legal, clinical, and investigative applications, making system robustness a key factor in routine operations.

Objectives and overview of the study

This study evaluated the operational stability and quantitation precision of the Agilent Ultivo triple quadrupole LC/MS system with a standard electrospray ionization source, coupled to an Agilent 1290 Infinity II LC. The system’s performance was tested for 26 target compounds spiked into human serum across six days, totaling 1,625 injections, to mimic high-throughput forensic workflows.

Methodology

Sample preparation included protein precipitation of human serum with cold acetonitrile, centrifugation, dilution, and spiking with drug standards. Calibration standards ranging from 2 to 50 ng/mL were run in triplicate at regular intervals. Dynamic multiple reaction monitoring (dMRM) was applied for data acquisition. Quality control samples (10 ng/mL) were interspersed every 100 injections to assess intra-run stability.

Used instrumentation

• Agilent 1290 Infinity II LC system with high-speed pump, multisampler plus cooler, and multicolumn thermostat.
• Agilent Ultivo triple quadrupole LC/MS with standard ESI ion source.
• Agilent MassHunter Quantitative Analysis software B.09 with Quant-My-Way feature for processing.

Main results and discussion

Across 1,400 QC injections, average relative standard deviations (RSD) were 4.3 % for raw peak area and 4.4 % for calculated concentration, demonstrating exceptional signal stability. Calibration curves maintained R² values ≥ 0.99 throughout 15 calibration sets over the six-day run. Only Δ9-THC showed notable degradation after 600 injections, highlighting compound-specific factors.

Benefits and practical applications

The compact design and early maintenance feedback of the Ultivo system minimize instrument downtime and support seamless capillary changes. Its robust performance under continuous operation makes it well suited for high-throughput forensic, clinical, and quality-control environments where large sample volumes and reliable quantitation are essential.

Future trends and potential applications

Continued improvements in ion source design and software automation will further enhance throughput and data integrity. Integration with laboratory information management systems and potential miniaturization of components may extend the method’s use to field-deployable toxicology screening and emerging forensic challenges.

Conclusion

The Agilent Ultivo LC/TQ with a standard ESI source paired with the 1290 Infinity II LC delivers outstanding robustness and reproducibility for multi-day, high-throughput drug analysis in serum. The system’s stability, accuracy, and reduced maintenance requirements offer clear advantages for demanding forensic toxicology workflows.

References

1. Sartain M, Sosienski T, Yang D. Robustness of the Agilent Ultivo Triple Quadrupole LC/MS for Routine Analysis in Food Safety. Agilent Technologies Technical Overview. Publication 5991-8741EN; 2017.
2. Grossman JN, Yang Y. Analytical Determination of Drugs in Serum Using the Ultivo Triple Quadrupole LC/MS. Agilent Technologies Application Note. Publication 5994-0056EN; 2019.