Gas chromatography-atomic emission detection for the measurement of isotopes. Application to bioequivalence studies.

This study was designed to demonstrate the ability of gas chromatography-atomic emission detection (GC-AED) to quantitatively measure amounts of labeled and unlabeled molecules when they are mixed together with both variable overall concentrations (labeled+unlabeled) and variable isotope ratios. To perform this study, simulations of bioequivalence trials were carried out using 13C stable isotopically labeled molecules (SIL) coadministered with the unlabeled drug to act as biological internal standards. Various methodological approaches are shown and different methods of calculation developed for the quantitative determination of both SIL and unlabeled molecules. The pharmacokinetic parameters experimentally obtained are quite in accordance with the target values and GC-AED appears to be a valuable alternative to mass spectrometry for this kind of trial with concomitant use of labeled and unlabeled molecules.