NOVEL MODIFICATIONS AND CLINICAL-APPLICATIONS OF PRECONCENTRATION-CAPILLARY ELECTROPHORESIS-MASS SPECTROMETRY

On-line capillary electrophoresis-mass spectrometry (CE-MS) is emerging as a powerful technique for the structural characterization of components of complex mixtures. However, its usefulness in the biomedical sciences is often precluded by poor concentration limits of detection (CLOD). Analytes of biological relevance are invariably not only components of complex mixtures, but are also present in extremely low concentrations. This paper demonstrates the novel use of C-18 impregnated and styrene-divinyl benzene copolymer membranes contained in a metal cartridge for analyte preconcentration (PC) on-line with CE-MS (PC-CE-MS). The paper describes how these elements, in conjunction with CE techniques (such as transient isotachophoresis), overcome some of the major limitations of PC-CE-MS (e.g., poor capillary efficiency, reduced electroosmotic flow (EOF), and inferior component resolution). The wide applicability of this new PC-CE-MS technology for the analysis of biomolecules is shown, and its usefulness in clinical studies by the direct analysis of patient urine is demonstrated for the detection of drug metabolites of the neuroleptic agent haloperidol, insulin-like growth factors in cell media, and protein fragments diagnostic of the disease state of multiple myeloma.