A Direct Method for the Determination of 13 Nitrosamines in Waterby LCMS-8045 System

Significance of the Topic

A variety of nitrosamines, notably N -nitrosodimethylamine (NDMA), are classified as probable human carcinogens and have been detected in drinking, recycled, and industrial waters due to disinfection and industrial processes. Conventional solid-phase extraction (SPE) methods face challenges with high organic loads, particulate-induced clogging, and potential analyte loss. A direct, robust analytical approach is therefore essential for accurate monitoring of trace nitrosamines in diverse water matrices.

Objectives and Study Overview

This work implements an ASTM D8456-compliant, direct liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify thirteen nitrosamines simultaneously in water without sample pretreatment. The study evaluates linearity, repeatability, recovery, and practical applicability of the method using a Shimadzu UHPLC Nexera XS hyphenated to an LCMS-8045 triple quadrupole mass spectrometer.

Methodology

Water samples spiked at four concentration levels (0.05, 0.10, 0.50, and 1.70 µg/L) were filtered and analyzed directly. Chromatographic separation was performed on a reversed-phase C18 column (150 × 4.6 mm, 5 µm) with a 0.1% formic acid water/methanol gradient at 0.7 mL/min and 40 °C. A diverter valve directed early eluent to waste and analyte window to the MS. Nitrosamines were ionized by atmospheric pressure chemical ionization (APCI) in positive mode, using multiple reaction monitoring (MRM) transitions optimized for each target and two deuterated internal standards (NDMA-d6, NDEA-d10). Calibration ranged from 0.05 to 5.00 µg/L with 1/C2 weighting.

Instrumentation

• UHPLC Nexera XS system, Shimadzu
• Triple quadrupole mass spectrometer LCMS-8045, Shimadzu
• Shim-pack GIST C18 column (150 mm × 4.6 mm, 5 µm)
• Atmospheric pressure chemical ionization interface

Main Results and Discussion

All thirteen nitrosamines exhibited excellent linearity (correlation coefficients > 0.99). Method repeatability at 0.05 µg/L yielded relative standard deviations below 13% for all analytes. Spiked recovery in synthetic effluent ranged from 59% to 135%, with most compounds recovered between 85% and 113%. The notably labile N ‑nitrosodiphenylamine (NDPhA) was monitored using an alternative m/z 170 precursor to avoid in-source fragmentation and ensure reliable quantification.

Benefits and Practical Applications

• Eliminates SPE cartridge clogging and analyte loss in high TOC/TSS waters
• Streamlined workflow with direct injection reduces preparation time
• High sensitivity and fast polarity switching enable sub-microgram detection
• Adaptable to environmental monitoring, industrial effluent testing, and pharmaceutical quality control

Future Trends and Potential Applications

Expanding the direct LC-MS/MS approach to additional nitrosamine analogs and more complex matrices such as wastewater, food extracts, and biological fluids can enhance comprehensive exposure assessments. Integration with high-resolution mass spectrometry and automated sample handling may further improve specificity, throughput, and lower detection limits for trace nitrosamine analysis.

Conclusion

A direct LC-MS/MS method on the Shimadzu LCMS-8045 platform was successfully developed for the simultaneous quantification of thirteen nitrosamines in water without sample pretreatment. The method offers robust linearity, precision, and recovery, providing a reliable alternative to traditional SPE-GC-MS workflows.

References

1. Krasner SW, Marfil-Vega R. Occurrence of nitrosamines and their precursors in North American drinking waters. AWWA Water Sci. 2020.
2. Thermal Electron Corporation. Instruction Manual Thermal Energy Analyzer TEA 502/LC. Waltham, MA, 1985.
3. Buglass AJ, Challis BC, Osborne MR. Transnitrosation and stability of N-nitrosodiphenylamine. IARC Sci Publ. 1974;94–100.