Stable isotope methodology in a pharmacokinetic study of the interaction of theophylline and cimetidine

Theophylline administered orally and (1, 3-15N,2-13C)theophylline administered intravenously in tracer quantities were used to investigate under steady-state conditions the interaction of theophylline with cimetidine in a patient with chronic obstructive pulmonary disease. Both compounds were quantified simultaneously by mass spectral-analysis after solvent extraction and high pressure liquid chromatographic purification of plasma samples. The assay is reliable and accurate to a plasma level of 50 ng mI−1 for the stable isotope tracer with a practical lower limit of detection of 10 ng mI−1.