10 μL CSR-LVSI with 5 ng Nitrosamines, THF, and 1,4-Dioxane On-Column

Significance of the Topic

Accurate quantification of trace nitrosamines alongside residual solvents such as tetrahydrofuran (THF) and 1,4-dioxane is critical in pharmaceutical quality control and environmental monitoring. These analytes pose health risks at low levels and require sensitive, reliable analytical techniques to ensure compliance with regulatory thresholds.

Study Objectives and Overview

This application note demonstrates a gas chromatography–mass spectrometry (GC–MS) method with selected ion monitoring (SIM) for simultaneous determination of nitrosamines and common solvent contaminants. A calibration mixture containing seven nitrosamines, THF, and 1,4-dioxane was injected on-column to evaluate chromatographic separation, detection sensitivity, and instrument performance.

Methodology and Instrumentation

• Column: Rxi-5Sil MS (30 m × 0.25 mm ID, 1.00 µm) with 10 m guard column.
• Sample: Nitrosamine calibration mix (Method 521) at 0.5 µg/mL, THF, and 1,4-dioxane in dichloromethane.
• Injection: 10 µL splitless (1.5 min hold) at 275 °C using a 4 mm single taper liner with wool.
• Oven program: 35 °C (1.5 min) → 50 °C at 50 °C/min (2.02 min) → 320 °C at 11.12 °C/min (1.5 min).
• Carrier gas: Helium at 5.08 mL/min constant flow.
• MS Detection: Agilent 5975C quadrupole MSD in SIM mode with solvent delay at 4.63 min; electron ionization; BFB tune.

Key Results and Discussion

• Retention times ranged from 4.6 min (1,4-dioxane) to 13.0 min (N-nitrosodi-n-butylamine), achieving clear resolution of all analytes.
• Sensitivity in SIM mode allowed detection of 5 ng on-column for each nitrosamine.
• The chromatogram exhibited distinct peaks for seven nitrosamines, THF, and 1,4-dioxane; a trace toluene contaminant was also observed.
• Mass fragments were selected to optimize quantitation while minimizing interferences, demonstrating robustness for low-level analysis.

Benefits and Practical Applications

• High sensitivity and selectivity for regulated nitrosamines in pharmaceutical and environmental samples.
• Efficient sample throughput with a total run time under 14 minutes.
• Minimal sample preparation due to direct injection approach, reducing potential losses and contamination.
• Compatibility with standard GC–MS instrumentation facilitates method adoption in routine laboratories.

Future Trends and Potential Applications

Continued development of capillary columns with tailored stationary phases may further enhance resolution of structurally similar nitrosamines. Integration with automated sample preparation and high-throughput GC–MS platforms could streamline regulatory compliance testing. Emerging ion mobility spectrometry and hybrid MS techniques may offer additional selectivity for complex matrices.

Conclusion

The described GC–MS SIM method on an Rxi-5Sil MS column provides a rapid, sensitive, and reliable approach for simultaneous determination of nitrosamines and key solvent contaminants. Its performance supports stringent quality control requirements in pharmaceutical manufacturing and environmental monitoring.

References

No external literature references were provided in the original document.