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 ml-1 for the stable isotope tracer with a practical lower limit of detection of 10 ng ml-1.