We developed a nanoreactor chip based system to mimic phase I metabolic reactions of small organic compounds. The microchip, made of silicon, has an anatase-phase titanium dioxide (TiO(2)) nanolayer coating for photocatalysis and an integrated electrospray ionization (ESI) tip for direct mass spectrometric (MS) analysis. This novel method for mimicking phase I metabolic reactions uses an on-chip TiO(2)-nanolayer and an external UV-lamp to induce photocatalyzed chemical reactions of drug compounds in aqueous solutions. The reactions of selected test compounds (verapamil, metoprolol, propranolol, lidocaine, 2-acetamidofluorene, and S-methylthiopurine) produced mostly the same main products as phase I metabolic reactions induced by human liver microsomes, rat hepatocytes, or cytochrome P enzymes, showing hydroxylation, dehydrogenation, and dealkylations as the main photocatalytic reactions. With this method it is possible to detect reactive and toxic products (mimicking reactive metabolites) due to the absence of biological matrices and an immediate analysis. The method used is sensitive: only 20-40 pmol (1-10 ng) of a substrate was needed for the experiment, thus it provides an inexpensive method for screening possible metabolites of new drug candidates. Due to small dimensions of the microchip, diffusion lengths are suitable for the high reaction rates, thus providing a rapid analysis as the reaction products can be detected and identified directly after the photoinduced reactions have occurred. The method shows a similar performance to that of electrochemistry, a commonly used technique for mimicking phase I metabolism.
Gas chromatography (GC) and ion trap mass spectrometry (MS) were combined with microchip atmospheric pressure chemical ionization (microAPCI) and microchip atmospheric pressure photoionization (microAPPI) sources. Selected polychlorinated biphenyls (PCBs, IUPAC Nos. 28, 52, 101, 118, 138, 153 and 180) were analyzed by GC/microAPCI-MS and GC/microAPPI-MS to demonstrate the applicability of the miniaturized ion sources in negative ion mode analysis. The microAPCI and microAPPI methods were evaluated in respect of detection limit, linearity and repeatability. The detection limits for the PCB congeners were somewhat lower with microAPCI than with microAPPI, whereas microAPPI showed slightly wider linear range and better repeatability. With both methods, the best results were obtained for highly chlorinated or non-ortho-chlorinated PCBs, which possess the highest electron affinities. Finally, the suitability of the GC/microAPPI-MS method for the analysis of PCBs in environmental samples was demonstrated by analyzing soil extracts, and by comparing the results with those obtained by gas chromatography with electron capture detection (GC/ECD).
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