Direct radiocarbon analysis of exhaled air

Abstract

Pharmacokinetic properties of organic substances in humans can be followed by isotopic labeling. For sub-milligram amounts, ¹⁴C becomes the preferable isotope and Accelerator Mass Spectrometry (AMS) its most powerful detection method. However, a widespread use of this method is partly impeded by laborious and time consuming sample preparation. We developed a method, which omits any preparation prior to AMS analysis, but allows direct measurement of CO₂. The method uses a zeolite molecular sieve for CO₂ trapping and requires a small gas interface, which is connected to a gas ion source of the AMS instrument. Based on the method, we developed a kit for CO₂ analysis in exhaled air. It can be used to monitor catabolism of labeled compounds to CO₂, a seldom studied route of elimination in pharmacokinetic studies. In addition, it provides an easy sampling method for breath tests as the erythromycin breath test, where the analysis with AMS would reduce the required ¹⁴C activity by ∼3 orders of magnitude. To demonstrate the potential of the kit in combination with the high sensitivity of AMS, we followed ethanol oxidation in human with a comestible: a brandy of 1964 vintage, enriched in ¹⁴C by ∼65% due to atmospheric nuclear bomb testing, could be used as labeled substance with an administered activity of ∼10 Bq¹⁴C only.