Analysis of diagnostic metabolites by capillary electrophoresis-mass spectrometry.

We describe here a procedure by capillary electrophoresis-mass spectrometry (CE-MS) for the direct analysis of urine samples on diagnostic metabolites, which are present in patient urine with metabolic disorders. The method was demonstrated using urine samples spiked with diagnostic metabolites, including glutathione for gamma-glutamyl transpeptidase deficiency, pyroglutamate for generalized glutathione deficiency, adenylosuccinate for adenylosuccinase deficiency, omithine for gyrate atrophy, histidine for histidinemia, and homogentisic acid for alcaptonuria, at concentrations similar to those found in patients' urine. A coaxial sheath liquid flow was used for coupling CE and MS in electrospray ionization mode. Identification of the metabolites is based on their molecular weights and fragmentation patterns. The CE-MS method is highly specific and sensitive comparing to the previously reported method using migration time and UV absorption for identification. It should find broad application in clinical and pharmaceutical research and development.