Application of Secondary Electrospray Ionization Coupled with High-Resolution Mass Spectrometry in Chemical Characterization of Thermally Generated Aerosols

Abstract

Inhalation as a route for administering drugs and dietary supplements has garnered significant attention over the past decade. We performed real-time analyses 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 (APIs) such as chloroquine, hydroxychloroquine, and azithromycin. This setup allowed us to detect caffeine, melatonin, hydroxychloroquine, chloroquine, and cannabidiol in the produced aerosols. Azithromycin and vitamin B12 in the aerosols could not be detected; however, our instrument setup enabled the detection of vitamin B12 breakdown products that were generated during the aerosolization process. Positive control was realized by liquid chromatography-HRMS analyses. 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 reveal the potential wide application of this technology for the real-time monitoring of aerosolized active pharmaceutical ingredients that can be administered through the inhalation route.

Applications of ambient ionization mass spectrometry in 2022: An annual review

“…122 Finally, another recent study utilized SESI-MS for the real-time detection of inhaled aerosols in exhaled breath for the purpose of studying the aerosolization performance of inhaled drug products. 123 The detection of pharmaceuticals in animals also has implications for environmental challenges. The presence of drug products in marine life can provide critical information regarding the contamination of water supplies and the effects of contaminating drugs in the body.…”

“…Several other studies have used DESI‐MS imaging to study the distribution of drugs in tissues, including acetaminophen and its metabolites in the mouse liver 121 and extracellular signal‐regulated kinase inhibitors in mouse brain tissues 122 . Finally, another recent study utilized SESI‐MS for the real‐time detection of inhaled aerosols in exhaled breath for the purpose of studying the aerosolization performance of inhaled drug products 123 …”

“… 122 Finally, another recent study utilized SESI‐MS for the real‐time detection of inhaled aerosols in exhaled breath for the purpose of studying the aerosolization performance of inhaled drug products. 123 …”

Data‐Driven Compound Identification in Atmospheric Mass Spectrometry

“…Samples do not need to be pre-treated, which enables direct, online analysis. While various methods exist for analyzing aerosols in real-time, such as resonance multiphoton ionization [59,60] and secondary electrospray ionization, [61] we will focus here on Api-CIMS due to its user-friendliness, reliability, and robustness. Api-CIMS can operate continuously for months, even in field conditions.…”

Elucidating the Role of Ion Suppression in Secondary Electrospray Ionization

“…Secondary electrospray ionization (SESI) is a highly sensitive and soft ambient ionization method. It is coupled with high-resolution mass spectrometry (HRMS) and can be used to detect and monitor a wide range of volatile and semivolatile organic compounds. − Although SESI offers many advantages (e.g., a higher sensitivity for polar and heavier compounds) compared to methods like selected-ion flow tube (SIFT) or proton-transfer reaction (PTR) mass spectrometry, it is still only semiquantitative. Quantification is possible only when calibration curves for specific metabolites can be obtained, which is time-consuming.…”