In recent years mass spectrometric detection has become more and more attractive in combination with separation methods such as liquid chromatography and electrophoretic techniques. Developments in interfacing have resulted in robust instrumental tools often based on the electrospray (ESP) principle or atmospheric pressure chemical ionization (APCI) enabling positive and negative ion detection. Both advanced strucuture elucidation in metabolism studies or pharmaceutical analysis such as impurity profiling and stability testing as well as routine bioanalytical work by LC-MS/MS, have demonstrated the enormous impact of this technology in R&D programs of the pharmaceutical industry. In the case of electrophoretic techniques the developments are still in progress and promising results are obtained but a major breakthough towards routine applications have not been achieved yet. Several novel routes however have opened the way to more robust applications especially in the bioanalytical field. Developments in the last 5 years have been achieved by applying isotachophoretic principles in combination with CE to increase the loadability of the system and to allow analysis of target compounds at low levels in biomatrices. Another electromigration based technology being developed is electro-elution combined with ITP/CE. In this case extraction from an organic solvent into a capillary is achieved by a voltage difference across the solvent and the capillary. In principle this is a two-step concentration technique, which is fast since the ITP time consuming step is performed after a considerable first volume reduction by the electro-extraction process.

Another approach taken to improve concentration sensitivity has been so-called pseudoelectrochromatography, which allows normal LC-principles to be combined with electromigration in packed fused-silica capillaries. Besides improvements in detection performance elegant control over selectivity can be achieved in such a set-up as demonstrated for the separation of sulphonamides. Compatibility limitations in mass spectrometric studies have especially been pronounced in the efforts combining micellar electrokinetic chromatography with mass spectrometry. The micelle containing buffer does not allow stable detection performance in the case of mass spectrometry. To overcome this limitation we have developed a coupled capillary approach in which a first capillary is operation in MEKC-mode and a second coupled capillary is operation in CE-mode with a suitable buffer for mass spectrometric detection. The development of MALDI has contributed greatly to the rapid development of biopolymer detection and characterization and the potential of this technique will be discussed using examples of peptide profiling in single cells and attomole detection in miniaturized systems.