T. Zivkovic Semren*, S. Majeed, M. Fatarova, C. Laszlo, C. Pak, S. Steiner, G. Vidal, A. Kuczaj, A. Mazurov, M. C. Peitsch, N. V. Ivanov, J. Hoeng, P. A. Guy

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)

Kolli, A.R., Semren, T.Z., Bovard, D. et al.

In vitro screening for pharmacological activity of existing drugs showed chloroquine and hydroxychloroquine to be effective against severe acute respiratory syndrome coronavirus 2. Oral administration of these compounds to obtain desired pulmonary exposures resulted in dose-limiting systemic toxicity in humans. However, pulmonary drug delivery enables direct and rapid administration to obtain higher local tissue concentrations in target tissue. In this work, inhalable formulations for thermal aerosolization of chloroquine and hydroxychloroquine were developed, and their physicochemical properties were characterized. Thermal aerosolization of 40 mg/mL chloroquine and 100 mg/mL hydroxychloroquine formulations delivered respirable aerosol particle sizes with 0.15 and 0.33 mg per 55 mL puff, respectively. In vitro toxicity was evaluated by exposing primary human bronchial epithelial cells to aerosol generated from Vitrocell. An in vitro exposure to 7.24 μg of chloroquine or 7.99 μg hydroxychloroquine showed no significant changes in cilia beating, transepithelial electrical resistance, and cell viability. The pharmacokinetics of inhaled aerosols was predicted by developing a physiologically based pharmacokinetic model that included a detailed species-specific respiratory tract physiology and lysosomal trapping.

M. T. Gaugg, A. Engler, Y. Nussbaumer-Ochsner, L. Bregy, A. S Stöberl, T. Gaisl, T. Bruderer, R. Zenobi, M. Kohler and P. M-L Sinues

The authors explore whether real-time breath research & analysis by SESI-HRMS is suitable to monitor changes at the metabolic level due to inhaling bronchodilator medication. The experimental results strengthen the notion that certain biochemical processes can be monitored.

P. M-L Sinues, M. Kohler, S. A. Brown, R. Zenobi and R. Dallmann

The time-of-day of drug application is an important factor in maximizing efficacy and minimizing toxicity. Real-time in vivo mass spectrometric breath analysis and research of mice was deployed to investigate time-of-day variation in ketamine metabolism. Different production rates of ketamine metabolites were found in opposite circadian phases.

Xue Li, P. M-L Sinues, R. Dallmann, L. Bregy, M.Hollmén, S. Proulx, S. A. Brown, M. Detmar, M. Kohler, and R. Zenobi

Noninvasive, real-time pharmacokinetic (PK) monitoring of ketamine, propofol, and valproic acid, and their metabolites was achieved in mice, using secondary electrospray ionization and high-resolution mass spectrometry. The PK profile of a drug influences its efficacy and toxicity because it determines exposure time and levels …

Gerardo Gamez, Liang Zhu, Andreas Disko, Huanwen Chen, Vladimir Azov, Konstantin Chingin, Gunter Kramerb and Renato Zenobi

Valproic acid pharmacokinetics and ingestion in humans can be monitored through a novel biomarker in exhaled breath.