Microdialysis is a relatively new sampling technique designed for the in vivo analysis of endobiotic/xenobiotic substances. The microdialysis probe is surgically implanted into a vein or a tissue of interest in an animal. Substances within the bloodstream or tissue with Mr below the molecular weight cutoff of the dialysis membrane dialyze across the membrane into the perfusate. We have interfaced this technique with mass spectral analysis using the coaxial continuous flow fast atom bombardment (CF-FAB) approach we have developed and tandem mass spectrometry. Our initial experiments have concentrated on the investigation of the half- life of the suspected carcinogen tris (2-chloroethyl)-phosphate in the blood of rats. Tris organophosphates have been widely used in plastics and synthetic fibers as flame retardants. We have determined the half- life of this compound in rats (introduced by injection into the blood stream) using both microdialysis/MS in anesthetized rats and in anesthetized and awake rats using conventional pharmacokinetic techniques. The free plasma concentration vs. time were analyzed by noncompartmental methods. There were definite statistical differences in the results obtained by the different methodologies. The microdialysis/MS results were similar to those reported for microdialysis/LC determinations of theophylline in anesthetized rats. We are currently investigating factors that might be responsible for the difference between the conventional vs. MD/MS methodology. Initial results indicate that problems with calibration of the MS response are primarily responsible rather than being due to differences in the sampling methodology.
