Analysis of Nine N-Nitrosamines Using Liquid Chromatography—High-Resolution, Accurate-Mass Mass Spectrometry

Significance of the topic

N-nitrosamines are potent mutagens and carcinogens found in water and various products. Reliable detection of trace levels in drinking water and wastewater is crucial for public health and regulatory compliance.

Goals and overview of the study

The study aimed to develop a fast, sensitive and robust UHPLC-HRAM-MS method to separate, identify and quantify nine N-nitrosamines in water matrices. It compared performance to the established GC-MS approach and validated the method in both ultrapure and environmental water samples.

Used instrumentation

• UHPLC system: Thermo Scientific Dionex UltiMate 3000 RSLC with Hypersil GOLD C18 column
• Mass spectrometer: Thermo Scientific Q Exactive hybrid quadrupole-Orbitrap operating in positive full-scan mode at 70,000 resolving power
• Software: Thermo Scientific Xcalibur and Dionex DCMSLink plug-in for data acquisition

Methodology and sample preparation

A methanolic stock solution containing nine N-nitrosamines and isotopically labeled internal standards (NDMA-d6, NDPA-d14) was prepared. Drinking and wastewater samples underwent solid-phase extraction following US EPA Method 521 but without SPE for ultrapure water. Internal standards were spiked prior to UHPLC-MS analysis.

Main results and discussion

The method resolved all analytes within six minutes. Instrumental detection limits ranged from 0.01 to 0.4 μg/L, and quantification limits from 0.05 to 1.0 μg/L in ultrapure water. In environmental samples, matrix-adjusted detection limits were between 0.4 and 12 ng/L. Extraction recoveries for eight target compounds ranged from 68% to 83%, exceeding the 52% efficiency of EPA Method 521. Calibration curves were linear (R² > 0.993) across relevant concentration ranges. Precision (RSD) was below 19% and accuracy bias within ±8.2%.

Benefits and practical applications

• High throughput: analysis completes in under six minutes per injection
• Minimal sample volume: 100 μL injection improves sensitivity for trace analysis
• Enhanced selectivity: accurate-mass detection reduces false positives in complex matrices

Future trends and potential applications

Advancements in orbitrap technology and data processing algorithms will further lower detection limits and expand analyte scope. Coupling with automated SPE and real-time monitoring could deliver rapid screening solutions for water treatment and food safety.

Conclusion

The UHPLC-HRAM-MS workflow offers a faster, more sensitive alternative to GC-MS for trace analysis of N-nitrosamines in water. Its robust performance across matrices supports its adoption for routine environmental monitoring and regulatory compliance.

References

• Munch JW. Method 521: Determination of Nitrosamines in Drinking Water by Solid-Phase Extraction and GC-MS/MS. US EPA; 2005.