Waters Xevo TQ Absolute-A highly sensitive LCMSMS for quantification of low concentration of seven Nitrosamine impurities

Importance of the topic

Nitrosamine impurities in pharmaceuticals pose significant risks due to their genotoxic and carcinogenic properties. Regulatory agencies mandate stringent monitoring at trace levels to ensure drug safety and compliance. Highly sensitive analytical methods are therefore critical to detect and quantify these compounds in complex matrices.

Objectives and study overview

This study aimed to optimize and evaluate the performance of the Waters Xevo TQ Absolute tandem quadrupole mass spectrometer coupled with an ACQUITY UPLC H-Class Plus system and Acquity Premier UPLC HSS T3 column. The focus was on quantifying seven common nitrosamines across a calibration range of 0.01 to 100 ng/mL, achieving robust sensitivity, linearity, and repeatability.

Methodology and Instrumentation Used

• LC conditions
  • Instrument: ACQUITY UPLC H-Class Plus
  • Column: Acquity Premier UPLC HSS T3, 1.8 µm, 2.1 × 100 mm
  • Mobile phase A: 5 mM ammonium formate/0.1% formic acid in water
  • Mobile phase B: 5 mM ammonium formate/0.1% formic acid in methanol
  • Run time: 15 min
• MS conditions
  • Instrument: Xevo TQ Absolute
  • Ionization: APCI positive mode
  • Cone voltage: 5–15 V; Corona voltage: 4.0 kV
  • Source temp: 120 °C; Probe temp: 250 °C
  • Desolvation gas: 800 L/h; Cone gas: 150 L/h
  • MRM transitions optimized for seven nitrosamines, with LOQ at or below 0.01 ng/mL

Key results and discussion

The method achieved limits of quantification at 0.01 ng/mL for all seven nitrosamines with excellent linearity (R² > 0.99) across the 0.01–100 ng/mL range. Six replicate injections demonstrated reproducible response, and matrix effects were minimized by the robust UPLC separation and optimized ionization conditions.

Benefits and practical applications

• Compliance with evolving regulatory limits by reaching ultra-low quantification thresholds.
• Consistent peak area and linear response ensure reliable routine analysis.
• Enhanced laboratory sustainability: up to 50% lower energy, gas, and heat consumption compared to similar instruments.

Future trends and potential applications

Advances may include automation of sample preparation, expansion to broader nitrosamine panels, and integration of real-time monitoring for continuous quality control. Improvements in source design and data processing algorithms will further enhance sensitivity and throughput.

Conclusion

The combination of Xevo TQ Absolute with ACQUITY UPLC H-Class Plus provides a highly sensitive, reliable, and sustainable platform for trace-level nitrosamine quantification. This workflow supports stringent regulatory requirements and offers practical benefits for pharmaceutical quality control.

References

1. Margaret Maziarz; Paul D. Rainville; Amy Bartlett. High Sensitivity Quantification of Nitrosamines in Metformin Using Xevo TQ Absolute Tandem Quadrupole Mass Spectrometer With an ACQUITY Premier System. Application Note: 720007725.