Utility of membrane preconcentration-capillary electrophoresis-mass spectrometry in overcoming limited sample loading for analysis of biologically derived drug metabolites, peptides, and proteins

Andy J. Tomlinson, Linda M. Benson, Stephen C Jameson, Douglas H. Johnson, Stephen Naylor

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

The limited loading of capillary electrophoresis (CE) leads to relatively poor concentration limits of detection. In this work a unique method for analyte preconcentration with capillary electrophoresis-mass spectrometry (CE-MS) is described. A cartridge containing an impregnated membrane is installed at the inlet of the CE capillary, and we term this 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 in molecular weight from 200-60,000 u. In particular, we describe the direct mPC-E-MS analysis of urine obtained from a patient receiving the neuroleptic drug haloperidol. Three metabolites were found in the urine, and two of them are implicated in the Parkinsonian-like side effects caused by taking this drug. The technique is also applied to the analysis 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 conjunction with either analyte stacking (small organic molecules such as metabolites) or moving-boundary transient isotachophoresis (peptides and proteins) after analytes have been eluted from the adsorptive membrane affords optimal performance and no compromise in CE mass spectrometry performance.

Original languageEnglish (US)
Pages (from-to)15-24
Number of pages10
JournalJournal of the American Society for Mass Spectrometry
Volume8
Issue number1
DOIs
StatePublished - Jan 1 1997

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