RESUMO
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.
Assuntos
Cafeína/análise , Isótopos de Carbono , Administração Oral , Disponibilidade Biológica , Cafeína/administração & dosagem , Cafeína/farmacocinética , Cromatografia Gasosa/métodos , Injeções Intravenosas , Modelos BiológicosRESUMO
Quantitation by gas chromatography-atomic emission detection (GC-AED) is based on the intensity of the signal measured at a wavelength characteristic of an element, after atomisation by the plasma. This response depends only on the number of atoms of this element present in the molecule under investigation, and is independent of the structure of the molecule. This technique was used for the assay of propofol, and the estimation of its two metabolites, after calibration with standard solutions of pure propofol. The results were compared with those obtained by gas chromatography-mass spectrometry (GC-MS). Propofol was quantified with higher precision and accuracy by GC-AED than by GC-MS which exhibited larger residual values. Concentration assessment for two metabolites showed a better agreement with the theoretical value by GC-AED since the response depends only on the number of carbon atoms in each molecule.