Quadrupole-based mass spectrometric evaluation of isotope ratios of carbon dioxide in expired air from mice and men following the administration of (13)C-methyl methionine

A method is described for the measurement of the isotopic ratio of (13)CO2/(12)CO2 in expired air from individual mice and from humans by means of a quadrupole-based mass spectrometer system. Following the administration of (13)C-methyl methionine or another appropriately labeled substrate, the (13)C portion of the molecule is converted to (13)CO2. The (13)CO2 enters the carbonate pool(s) and is ultimately eliminated in the expired air where it is available for analysis. The expired air is transported by a small pump from the subject to a digital valve which provides for the alternate influx of expired air and standard into the mass spectrometer for 30 or 60 seconds each, respectively. The inlet consists of a control valve connected to a microbore stainless steel tube, and can be adjusted manually to achieve a source pressure of 4 X 10(-5) torr. The correction factors for drift in sensitivity and in the mass axis are generated by repeated, automatic analysis of the running standard and relating those measurements to values generated for the standard during the first minutes of the experiment. Each measurement of an isotopic ratio in expired air is corrected by an amount determined by the standard immediately preceding it. Precision for the measurements of both sample and standard ratios is ±0.2%. The technique should prove useful in assessing the metabolism, of substrates that are converted to CO2 and may find utility as a diagnostic tool for certain diseases and metabolic disorders.