Flow injection with chemical reaction interface-isotope ratio mass spectrometry: an alternative to off-line combustion for detecting low levels of enriched 13C in mass balance studies

We have evaluated the potential of flow injection chemical reaction interface isotope-ratio mass spectrometry to replace radioactive labeling techniques in material balance studies. A sample is flow injected and transmitted through a desolvation system followed by combustion to form ¹³CO₂ with a microwave-powered chemical reaction interface. We can detect trace amounts of a ¹³C-labeled drug (3′-azido-3′-deoxythymidine, AZT) in urine or feces. Our ability to quantify less than 100 ng/mL of excess ¹³C (∼1 μg/mL of ¹³C-labeled AZT) from a sample equivalent to 10 μL of urine is superior to previous detection limits for ¹³C in urine that use off-line combustion methods. Parallel studies using ¹⁴C-labeled AZT showed that our stable isotope method provides comparable percent excretion data for urine and feces. These results support previous findings that mass balance studies could be carried out with isotope-ratio mass spectrometer, here using doses as low as 1–2 mg/kg.