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 (FCSI)‐mass spectrometry (MS), was characterized towards trace‐level residue screening of select NAMs (e.g., N ‐nitrosodimethylamine, N ‐nitrosodiethylamine, N ‐nitrosodibutylamine) directly from complex and problematic matrices of interest, including prescription and over‐the‐counter tablets, drinking water, soil, and consumable goods. Spectral data for analyte confirmation and detection limit studies were collected using a Thermo LCQ Fleet ion trap mass spectrometer. Results PSI‐MS and FCSI‐MS readily produced mass spectral data marked by their simplicity (e.g., predominantly protonated molecular ions observed) and congruence with traditional electrospray ionization mass spectra in under 2 min. per sample. Both methods proved robust to the complex matrices tested, yielding ion signatures for target NAMs, as well as active pharmaceutical ingredients for analyzed tablets, flavorants inherent to food products, etc. Low part‐per‐million 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.

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.

Significant efforts have went towards coupling portable mass spectrometric systems and ambient ionization methods, with a culminating goal of field-based, point-of-need screening of harmful chemicals. While fieldable, ambient MS methods are an intriguing combination, ruggedness of these ionization methods in regard to naturally-occurring environmental conditions while operating in-situ, such as ambient temperature, relative humidity (RH) and wind, bears further investigation, as such reports are limited. In this work, a systematic characterization of paper spray ionization-mass spectrometry (PSI-MS) performance under variable environmental conditions was undertaken on a field-deployable MS system. Of all conditions, the presence of wind speeds greater than 3 m/s (~7 MPH) was shown to have the most substantial effect on the spectral attributes of signal intensity and duration of the PSI-MS spraying event. Generally, moderate ambient temperature and %RH produced the best spectral performance for PSI-MS. Heat maps were generated from field-collected data across variable temperature and %RH in an effort to inform general PSI-MS performance trends and guide on-site operation by potential users.(c) 2021 Elsevier B.V. All rights reserved.

Cover: REIMS applica ons to direct ssue analysis ex vivo and in vivo.(a) Applica ons of REIMS for ex vivo cancer diagnosis using an electrosurgical handpiece coupled to an MS system with a heated coil interface.

Mass spectrometry is commonly used in forensic chemistry laboratories for sensitive, definitive analysis. There have been significant efforts to bring mass spectrometry analysis on-site through the development of ruggedized, fieldable instruments. Testing samples in the field is of particular interest in forensic science, homeland security, and defense applications. In forensic chemistry, testing seized drugs in the field can significantly improve efficiencies in processing of related criminal cases. The screening of passengers and luggage at transportation hubs is a critical need for homeland security for which mass spectrometry is well suited to provide definitive answers with low false positive rates. Mass spectrometry can yield reliable data for military personnel testing sites for potential chemical weapons release. To meet the needs of the forensic and security communities fieldable mass spectrometers based on membrane inlet systems and hybrid gas chromatography systems have been developed and commercialized. More recently developed ambient ionization mass spectrometry methods can eliminate the time, equipment, and expertise associated with sample preparation, and so are especially appealing for on-site analysis. We describe the development of fieldable mass spectrometry systems, with emphasis on commercially available systems that have been deployed for on-site analysis of seized drugs, chemical warfare agents, explosives, and other analytes of interest to the forensic and security communities. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.