Systematic development of on-line membrane preconcentration-capillary electrophoresis-mass spectrometry for the analysis of peptide mixtures. 
A unique method for analyte preconcentration on-line with CE and CE-mass spectrometry (CE-MS) that can concentrate large sample volumes (> 100 microL) is described.  A cartridge containing a suitably impregnated membrane is installed at the inlet of the CE capillary, and this approach is termed membrane preconcentration-CE-MS (mPC-CE-MS).  The authors describe the mPC-CE-MS analysis of dilute peptide mixtures (approximately 1 fmol/nL) that are concentrated onto the membrane and subsequently subjected to on-line sample cleanup prior to elution and ultimately CE-MS.  The systematic development of mPC-CE-MS is demonstrated, and the necessity of minimizing the adsorptive phase in order to ensure efficient peptide analyte recovery and minimization of organic elution solvent is described.  The authors compare and contrast mPC-CE and mPC-CE-MS with PC-CE and solid-phase preconcentration-CE-MS (PC-CE-MS), and describe several limitations of the latter approach, which includes analyte zone broadening and compromised analyte resolution.  Finally, the authors show that the use of mPC-CE-MS in conjunction with transient isotachophoresis after the peptides have been eluted from the adsorptive membrane affords optimal performance, and theoretical plate values of up to approximately 2.6 x 10(6) are observed for the analysis of a nine-component peptide mixture using this approach.  It is conservatively estimated that, in conjunction with an MS array detector, a practical concentration limit of detection (CLOD) for peptides is approximately 500 fg-1 pg/mL using mPC-CE-MS.