Rapid Screening of High Priority N‐Nitrosamines in Pharmaceutical, Forensic, and Environmental Samples with PSI‐MS and FCSI‐MS

Rationale

The burgeoning concern of N-nitrosamine (NAM) contamination found in various pharmaceutical compositions has increased the demand for rapid and reliable screening methods to better assess the breadth of the problem. These carcinogenic compounds are also found in food, water, and soil, and they have been used in poison-related homicides.

Methods

A combination of complementary, ambient ionization methods, paper spray ionization (PSI) and filter cone spray ionization-mass spectrometry (FCSI-MS), was characterized towards trace-level residue screening of select NAMs (e.g., NDMA, NDEA, NDBA) directly from complex and problematic matrices of interest, including prescription and OTC tablets, drinking water, soil, and consumable goods. Spectral data for analyte confirmation and detection limit studies were collected on a Thermo LCQ Fleet ion trap mass spectrometer.

Results

PSI-MS and FCSI-MS readily produced mass spectral data marked by its simplicity (e.g., predominantly protonated molecular ions observed) and congruence with traditional ESI-MS spectra in under 2 minutes/sample. Both methods proved robust to the complex matrices tested, yielding ion signatures for target NAMs, as well as active pharmaceutical ingredients (APIs) for analyzed tablets, flavorants inherent to food products, etc. Low part-per-million (ppm) detection limits were observed but were shown dependent on sample composition.

Conclusions

PSI-MS and FCSI-MS were successful in detecting trace-level NAMS in complex liquid- and solid-phase matrices with little to no prior preparation. This work suggests that these methodologies can provide a means for assessing problematic pharmaceutical adulterants/degradants for expedited quality control, as well as enhancing environmental stewardship efforts and forensic investigations.