Exhaled breath analysis of non-volatile drugs: Towards clinical applications

Exhaled breath is a promising specimen for in vivo drug analysis. The analysis of non-volatile drugs (NVDs) in exhaled breath is especially valuable due to the clinical prevalence of NVDs. NVDs transfer from the body to the exhaled air in the form of exhaled breath particles (EBPs). The generation of EBPs involves multiple sites in the respiratory tract and complex mechanisms linked to breathing maneuvers. The exhaled NVDs concentrations typically fall within the range of pg L-1, presenting significant analytical challenges. Breath analysis for NVDs finds utility in drugs of abuse testing and therapeutic drug monitoring, with a growing body of related studies. This review thoroughly describes the origin of NVDs in exhaled breath, and summarizes the characteristics and limitations of current analytical methods for exhaled NVDs, as well as the applications of breath analysis for NVDs, in order to provide helpful guidance for subsequent basic and translational research.