Mass spectrometry based fragmentation patterns of nitrosamine compounds.

Abstract

Nitrosamines are a class of mutagenic substances that can display high carcinogenic potential. New chemical entities may have the potential to form unique nitrosamines specific to the drug substance. It is therefore essential to understand the gas-phase fragmentation behavior of nitrosamine compounds to enable the development of analytical methods to characterize novel nitrosamine compounds. The gas-phase fragmentation behavior of eight model nitrosamine compounds representing the common substructures seen in many small molecule pharmaceutical compounds was studied with positive electrospray ionization tandem mass spectrometry (ESI-MS/MS). The fragmentation patterns of these compounds under various collision parameters available in commercially available mass spectrometers were studied. Protonated nitrosamine compounds produced diagnostic fragment ions upon MS/MS. Three primary structure-dependent fragmentation pathways were observed. The first pathway involves the loss of 30 Da which corresponds to the loss of the NO radical from the protonated nitrosamine compound (Group 1). The second and third fragmentation pathways, which have not been reported for nitrosamine compounds, proceed via the loss of H2 O from the protonated nitrosamine compound (Group 2), and elimination and a loss of 46 Da (loss of NH2 NO) from the nitrosamine compound (Group 3). Results presented in this work provide an overview of the gas-phase fragmentation patterns of nitrosamine compounds and may be useful in identifying novel nitrosamine compounds in complex matrices.