UTILITY OF MEMBRANE-PRECONCENTRATION CAPILLARY-ELECTROPHORESIS MASS-SPECTROMETRY IN OVERCOMING LIMITED SAMPLE LOADING FOR ANALYSIS OF BIOLOGICALLY DERIVED DRUG METABOLITES, PEPTIDES, AND PROTEINS

The limited loading of capillary electrophoresis (CE) leads to relativ ely poor concentration limits of detection. In this work a unique meth od for analyte preconcentration with capillary electrophoresis-mass sp ectrometry (CE-MS) is described. A cartridge containing an impregnated membrane is installed at the inlet of the CE capillary, and we term t his approach membrane preconcentration capillary electrophoresis-mass spectrometry (mPC-CE-MS). The analysis of in vivo derived metabolites, peptides, and proteins is described showing the wide applicability of the technology in the analysis of numerous compound classes ranging i n molecular weight from 200-60,000 u. In particular, we describe the d irect mPC-CE-MS analysis of urine obtained from a patient receiving th e neuroleptic drug haloperidol. Three metabolites were found in the ur ine, and two of them are implicated in the Parkinsonian-like side effe cts caused by taking this drug. The technique is also applied to the a nalysis of major histocompatibility complex class I peptides obtained from EG-7 cells. Furthermore, the clinical potential of this approach is described by the direct analysis of urine from a patient suffering from multiple myeloma, as well as aqueous humor derived from a patient undergoing surgery. Finally we show that the use of mPC-ME-MS in conj unction with either analyte stacking (small organic molecules such as metabolites) or moving-boundary transient isotachophoresis (peptides a nd proteins) after analytes have been eluted from the adsorptive membr ane affords optimal performance and no compromise in CE mass spectrome try performance. (C) 1997 American Society for Mass Spectrometry