Low Level Detection of N-nitrosodimethylamine Using Gas Chromatography Coupled with Orbitrap-based Mass Spectrometry

Significance of the Topic

Trace levels of N-nitrosodimethylamine (NDMA) in drinking water pose significant health risks due to its potent carcinogenicity even at concentrations near 0.01 µg/L. Reliable detection and quantification of NDMA are essential for regulatory compliance and human safety, as NDMA forms as a by-product during chloramination in water treatment processes.

Aims and Overview of the Study

This work evaluates a high-resolution gas chromatography–Orbitrap mass spectrometry (GC-Orbitrap MS) method to achieve low-level detection of NDMA. The study assesses sensitivity, mass accuracy, repeatability and linearity using solvent standards that simulate sample extracts, aiming to demonstrate full-scan capabilities for retrospective data review.

Methodology and Instrumentation

A Thermo Scientific Q Exactive GC hybrid quadrupole-Orbitrap MS was coupled to a TRACE 1310 GC with a TraceGOLD TG-200 ms column (30 m × 0.25 mm × 0.25 µm). Sample introduction employed a TriPlus RSH autosampler in surged splitless mode. The Orbitrap was tuned with PFTBA for <0.5 ppm mass accuracy at 60 000 resolving power (FWHM at m/z 200). Calibration standards ranged from 0.1 to 100 µg/L NDMA in dichloromethane, each spiked with 20 µg/L d6-NDMA as internal standard.

Main Results and Discussion

• Chromatographic Separation and Resolution: Fast GC achieved clear separation of NDMA at 0.1 µg/L with well-defined peaks. Orbitrap resolving power >100 000 at m/z 74 prevented interference from background ions.
• Instrument Detection Limit (IDL) and Repeatability: The IDL was 0.09 µg/L based on nine injections of the 0.1 µg/L standard. Peak area repeatability (%RSD) was below 5 % for d6-NDMA over 33 injections and below 3 % for NDMA at key levels.
• Mass Accuracy: Measured mass errors for the NDMA molecular ion (m/z 74.04747) remained below 1 ppm across the concentration range.
• Linearity of Response: Calibration across 0.1–100 µg/L exhibited linear regression R2 > 0.999 and relative response factor variability (%RSD) below 16 %.

Practical Benefits and Applications

The GC-Orbitrap MS method offers high sensitivity and selectivity for trace NDMA, with full-scan data enabling detection of additional contaminants and retrospective analysis. The robust repeatability and sub-ppm mass accuracy facilitate confident quantification in regulatory and research laboratories.

Future Trends and Potential Applications

Future work should extend validation to real drinking and wastewater matrices, explore automation for high-throughput monitoring, and integrate Orbitrap workflows for multi-analyte screening of nitrosamines and related emerging contaminants.

Conclusion

This study demonstrates that GC-Orbitrap MS delivers low-level NDMA detection down to 0.1 µg/L with excellent mass accuracy, repeatability and linearity. The platform’s full-scan capability supports comprehensive water quality screening while meeting the sensitivity demands for regulatory compliance.

References

• Mitch WA et al. N-nitrosodimethylamine (NDMA) as a drinking water contaminant: A review. Environmental Engineering Science 20(5):389–404 (2003)
• Sedlak DL et al. Sources and fate of nitrosodimethylamine and its precursors in municipal wastewater treatment plants. Water Environment Research 77(1):32–39 (2005)
• U.S. EPA Method 521, Determination of Nitrosamines in Drinking Water by SPE and GC-CI-MS/MS (2004)