We have developed an on-line analytical system involving microdialysis (MD) sampling, a carbohydrate membrane desalter (CMD), and an inductively coupled plasma mass spectrometer (ICPMS) system for the simultaneous determination of multiple trace metals in the extracellular fluid (ECF) in the brains of anesthetized rats. The microdialysate that perfused from the animal at a flow rate of 0.5 microL/min was on-line transferred to the CMD to remove the high-sodium matrix, followed by ICPMS measurement. The role of the CMD in this on-line system was investigated in detail. With prior addition of EDTA to the microdialysate to form anionic complexes of the metal analytes and the use of NH4Cl as a regenerant to exchange Na(+) with NH4(+) ions, both quantitative recovery of the trace metal analytes and quantitative removal of the sodium matrix could be achieved. Two experimental modes of the monitoring system were constructed. For those metals (e.g., Cu, Zn, and Mn) that existed at (sub)nanogram-per-milliliter concentrations in the microdialysate, the temporal resolution was 10 min when using a 10 microL loop for sample collection, followed by CMD and ICPMS; for those elements (e.g., Ca and Mg) that existed at microgram-per-milliliter levels (or greater), near-real-time analysis was possible because the microdialysate could be led, bypassing the sample loop, directly to the CMD for desalting without any time delay. Further improvement of the temporal resolution for the low-concentration elements was not possible without decreasing the detection limits of mass detection. Among the eight trace metals tested using this on-line system, the method detection limits for Cu, Zn, Mn, Co, Ni, and Pb reached subnanogram-per-milliliter levels; for electrolyte species such as Ca and Mg, the detection limits were in the range of 50-100 ng/mL. Analytical accuracy, expressed as spike recovery, was 100% +/- 15% for all of the elements tested. We demonstrate the applicability of the proposed system through the successful measurement of the basal values of Ca, Mg, Cu, Zn, and Mn in the ECF of a living rat brain and through in vivo monitoring of the concentration profiles of Mn and Pt in the ECF after the injection of drugs (MnCl2 and cisplatin) into the rats. This microdialysis system is the first to offer real-time, in vivo monitoring of trace elements such as Ca and Mg.

To study the permeability of the blood-brain barrier (BBB) to arsenates, arsenite, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), molybdate, and methylmercury, and the transfer behavior of these species, we constructed an automatic online analytical system comprising a microdialysis sampling device, a minicolumn packed with nonfunctionalized poly(vinyl chloride) beads, and an inductively coupled plasma mass spectrometer for continuous in-vivo measurement of their dynamic variation in the extracellular space of the brains of living rats. By using ion-polymer interactions as a novel working mechanism for sample pretreatment of volume-limited microdialysate, we simplified the operating procedure of conventional solid-phase extraction and reduced the contribution to the blank of the chemicals used. After optimizing this hyphenated system, we measured its performance by analysis of NIST standard reference materials 1640a (trace elements in natural water) and 2672a (trace elements in human urine) and by in-vivo monitoring of the dynamic variation of the compounds tested in the extracellular fluid (ECF) of rat brain. We found that intraperitoneal administration led to observable BBB permeability of arsenates, arsenite, DMA, MMA, and molybdate. Nevertheless, the limited sensitivity of the system and the size of microdialysis samples meant that detection of MeHg in ECF remained problematic, even when we administered a dose of 20 mg MeHg kg(-1) body weight. On the basis of these practical demonstrations, we suggest that our analytical system could be used not only for dynamic monitoring of the transfer kinetics of the four arsenicals and molybdate in the rat brain but also to describe associated neurotoxicity in terms of exposure to toxic metals and their species.