First report on the pharmacokinetics of tramadol and O-desmethyltramadol in exhaled breath compared to plasma and oral fluid after a single oral dose

[Display omitted] Exhaled breath (EB) is a promising matrix for bioanalysis of non-volatiles and has been routinely implemented for drugs of abuse analysis. Nothing is known regarding the pharmacokinetics of therapeutics and their metabolites in EB. Therefore, we used tramadol as a model drug. Twelve volunteers received a single oral dose of tramadol and repeated sampling of EB, plasma, and oral fluid (OF) was done for 48h using a particle filter device for EB and the Quantisal-device for OF. Samples were analyzed with LC–MS/MS and the pharmacokinetic correlations between matrices were investigated. The initial tramadol half-life in EB was shorter than in plasma but it reappeared in EB after 8–24h. The ratio of O-desmethyltramadol to tramadol was considerably lower in EB and OF compared to plasma. This pilot study compared for the first time the pharmacokinetics of a therapeutic drug and active metabolite in different biomatrices including EB and demonstrated its potential for bioanalysis.