Determination of¹³CO₂/¹²CO₂Ratio by IRMS and NDIRS

Abstract

Breath tests using (13)C-labelled substrates require the measurement of (13)CO(2)/(12)CO(2) ratio in breath gas samples. Next to isotope ratio mass spectrometry (IRMS), which is very sensitive but also complex and expensive, alternatively isotope selective nondispersive infrared spectrometry (NDIRS) can be used to determine the (13)CO(2)/(12)CO(2) ratio in expired breath. In this study we compared NDIRS- with IRMS-results to investigate whether the less expensive and very simply to operate NDIRS works as reliable as IRMS. For this purpose we applicated 1-(13)C-Phenylalanine to patients with advanced liver cirrhosis and healthy volunteers and took duplicated breath samples for IRMS and NDIRS at selected time points. Our data show a good correlation between these two methods for a small number of samples as required for simple breath tests. Longer series, where repeated measurements are required on the NDIRS instrument lead to a decreasing correlation. This indicates the superiority of IRMS concerning (13)CO(2)-kinetics over longer time periods.

Applications of stable isotopes in clinical pharmacology

“…When molar isotope enrichments are below 0.1%, isotope ratio mass spectrometry (IRMS) must be applied [11]. This type of MS determines isotope ratios at the atomic level ( 13 15 N/ 14 N). Isotope ratio mass spectrometry originates from geochemistry, where minor differences of isotopes at the natural abundance level are to be detected to determine the origin of, for instance, fossils.…”

“…Breath may be introduced directly into the IRMS after GC separation of the breath gases (O2, N2 and CO2). Recently, a nondispersive infrared technology was developed and applied routinely to measure 13 C abundance in breath CO2 [12,13]. When nongaseous molecules are to be measured, GC can be coupled to the IRMS by a capillary reaction interface.…”

“…Gas chromatography may be coupled directly to the IRMS for breath analysis (e.g. 13 C/ 12 C in breath CO2). For this purpose, different options are available.…”

“…Administration of 13 C-labelled endogenous substances, such as carbohydrates and lipids, has been widely applied in biochemical studies but to our knowledge never induced intoxication, either when administered as a single oral dose or as a continuous intravenous infusion. In practice, when designing an experiment, the dose of a labelled endogenous substance will be chosen between the limit of detection and 10% of …”

“…Stable isotopes are not radioactive and may be incorporated in molecules that can be traced by analytical techniques discriminating on molecular weights (Table 2). An example of a stable isotopically labelled molecule is 13 C-urea, in comparison to the naturally occurring 12 C-urea, having molecular weights of 61.06 and 60.06 g mol -1 , respectively. In this case, the mass of the labelled molecule is only modestly increased (1.7%).…”