Analysis of nine N-nitrosamines using liquid chromatography-accurate mass high resolution-mass spectrometry on a Q-Exactive instrument

Abstract

A selective and robust methodology for the analysis of nine N-nitrosamines (NAs), N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMor), N-nitrosomethylethylamine (NMEA), N-nitrosopyrrolidine (NPyr), N-nitrosodiethylamine (NDEA), N-nitrosopiperidine (NPip), N-nitroso-n-dipropylamine (NDPA), N-nitrosodi-n-butylamine (NDBA) and N-nitrosodi-n-phenylamine (NDPhA), was developed and validated. This method is based on ultra-high-performance liquid chromatography (UHPLC) coupled to mass spectrometry using heated electrospray ionization (HESI) in positive ionization mode with a Q-Exactive mass spectrometer. After the selection of a suitable column for NA separation, the mobile phase and the injection volume as chromatography parameters were optimized. Mass spectrometry operating parameters, including sheath gas, auxiliary gas, spray voltage, S-Lens RF Level, resolution, automatic gain control (AGC) target and maximum injection time, were also optimized in order to maximize the instrument analytical signal response. The method was optimized and validated in HPLC grade water, drinking water and wastewater matrices with satisfactory results. For accurate quantification, NDMA-d₆ and NDPA-d₁₄ were used as internal standards. The extraction recoveries in real matrices ranged from 68–83% for eight of the nine target nitrosamines, except for NDPhA with values of 22–31%. The detection limits ranged from 0.4 to 12 ng L⁻¹. Analytical results revealed a trace concentration of NDPhA (1.2 ng L⁻¹) in one of the analyzed water matrices. This work demonstrates that nitrosamines can be analyzed using LC-MS, on a Q-Exactive instrument, offering a faster alternative to the traditional GC-MS methods. The use of high resolution accurate mass spectrometry helps to obtain good selectivity for the detection of both GC-detectable and GC-undetectable compounds.