Real-Time Chemical Characterization of Aerosols by Secondary Electrospray Ionization Coupled with High-Resolution Mass Spectrometry
Tanja Zivkovic Semren*, Shoaib Majeed, Maria Fatarova, Csaba Laszlo, Claudius Pak, Sandro Steiner, Guillermo Vidal, Arkadiusz Kuczaj, Anatoly Mazurov, Manuel C. Peitsch, Nikolai V. Ivanov, Julia Hoeng, Philippe A. Guy
Abstract
Inhalation as a route for administering drugs and dietary supplements has garnered significant attention over the last decade. We performed real-time analysis of aerosols using secondary electrospray ionization (SESI) technology interfaced with high-resolution mass spectrometry (HRMS), primarily developed for exhaled breath analysis with the goal to detect the main aerosol constituents. Several commercially available inhalation devices containing caffeine, melatonin, cannabidiol, and vitamin B12 were tested. Chemical characterization of the aerosols produced by these devices enabled detection of the main constituents and screening for potential contaminants, byproducts, and impurities in the aerosol. In addition, a programmable syringe pump was connected to the SESI–HRMS system to monitor aerosolized active pharmaceutical ingredients (API), such as chloroquine, hydroxychloroquine, and azithromycin. This setup allowed us to detect caffeine, melatonin, hydroxychloroquine, chloroquine, and cannabidiol in the produced aerosols ; vitamin B12 and azithromycin in the aerosols could not be detected. Positive control was realized by liquid chromatography-HRMS analyses. However, our instrument setup enabled the detection of the breakdown products of vitamin B12 that were generated during the aerosolization process. The compounds detected in the aerosol were confirmed by exact mass measurements of the protonated and/or deprotonated species, as well as their respective collision-induced dissociation tandem mass spectra. These results indicate the potential wide application of this technology for the real-time monitoring of aerosolized APIs that can be administered through the inhalation route.
Keywords: Aerosol characterization, Direct aerosol analysis, Drug aerosolization, Exhaled breath, Inhalation drug delivery, Secondary electrospray ionization-high-resolution mass spectrometry