Analytical methodology to determine stable isotopically labelled and unlabelled theophylline in human plasma using capillary gas chromatography-mass spectrometry.

A method is described for the simultaneous determination of [1,3-15N] theophylline and unlabelled theophylline in human plasma using gas chromatography-mass spectrometry. Plasma samples were subjected to extractive alkylation and the stable isotopically labelled and unlabelled forms of the drug were analysed as their N-pentafluorobenzyl derivatives on an SE-52 fused-silica capillary column. Quantitation was made by selected-ion monitoring employing as the internal standard 3-isobutyl-1-methylxanthine. The method has been used to study the absorption kinetics and bioavailability of a sustained release formulation of the drug when co-administered to human volunteers with a conventional formulation of the drug labelled with the stable isotope.