Finding NDMA Precursors Using Accurate Mass Tools with an Agilent 6540 Q-TOF LC/MS

Importance of the Topic

NDMA is a potent nitrosamine disinfection by-product with significant health risks detected in chloraminated drinking water and treated wastewater. Its formation depends on reactions between chloramines and unknown organic precursors, making the identification of these precursors essential for effective water treatment and regulatory compliance.

Aim and Overview of the Study

This work applied high-resolution Q-TOF LC/MS and Agilent MassHunter accurate mass tools to discover both known and novel NDMA precursors. Three complementary screening approaches were used to mine treated drinking water and wastewater samples for compounds capable of forming NDMA under chloramination.

Methodology and Instrumentation

Screening workflows:

• PCDL library search of 66 known or suspected NDMA precursors using accurate mass and retention time.
• Neutral loss detection of 45.0578 Da corresponding to loss of the dimethylamine moiety during Auto MS/MS.
• Diagnostic ion extraction of m/z 58.0651 produced by β-cleavage at the tertiary dimethylamine structure using All Ions acquisition.

Sample preparation:
Surface water from the South Platte River and secondary-treated wastewater from Mesa, Arizona were concentrated by cation-exchange SPE at pH 3 and eluted with 5 % NH₄OH in methanol.

Instrumentation:

• Agilent 1290 Infinity UHPLC system
• ZORBAX Eclipse XDB-C8 column (150 × 4.6 mm, 3.5 µm)
• Agilent 6540 Q-TOF LC/MS with MassHunter v6.01 software

Main Results and Discussion

PCDL screening identified 11 known precursors including metformin, diuron, diphenhydramine, ranitidine, azithromycin, and others. Neutral loss analysis in the Mesa wastewater revealed methadone as a previously unrecognized NDMA precursor through a characteristic 45.0578 Da loss from m/z 310.2152 to m/z 265.1577. Diagnostic ion extraction confirmed tertiary dimethylamine fragments at m/z 58.0651 in both surface and wastewater samples. MS/MS spectra matched methadone against the forensic PCDL library, and standard verification showed methadone yields up to 58 % molar conversion to NDMA under chloramination.

Benefits and Practical Applications

This integrated accurate mass approach enables rapid, non-targeted discovery of NDMA precursors in complex water matrices. The neutral loss and diagnostic ion methods streamline screening for tertiary amine structures without exhaustive reference standards. Quantitative data on methadone and other precursors support targeted risk assessments and optimization of treatment processes to minimize NDMA formation.

Future Trends and Potential Applications

Expansion of PCDLs and automated data workflows will accelerate identification of emerging nitrosamine precursors. Coupling HRMS with ion mobility or orthogonal fragmentation techniques can enhance confidence in structure elucidation. Applying these methods to broader nitrosamine classes and diverse environmental samples will provide comprehensive contaminant profiling and inform regulatory strategies.

Conclusion

Agilent accurate mass Q-TOF LC/MS combined with PCDL screening, neutral loss detection, and diagnostic ion extraction proved effective for identifying known and novel NDMA precursors in drinking water sources and wastewater. Methadone emerged as a significant contributor to NDMA formation, demonstrating the value of this methodology for environmental monitoring and water treatment optimization.

References

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