title: Newborn screening of inborn errors of metabolism by capillary electrophoresis-electrospray ionization-mass spectrometry: a second-tier method with improved specificity and sensitivity.
abstract: The advent of electrospray-ionization mass spectrometry (ESI-MS) has given rise to expanded newborn screening programs for the early detection of inborn errors of metabolism (IEM). Despite the benefit of high-throughput screening for disease prognosis, conventional ESI-MS methods are limited by inadequate specificity, complicated sample handling, and low positive predictive outcome that can contribute to a high rate of false-positives. Herein, we report a robust strategy for neonatal screening based on capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) that offers a convenient platform for the direct analysis of amino acids, acylcarnitines, and their stereoisomers from dried blood spot (DBS) extracts without chemical derivatization. On-line sample preconcentration with desalting by CE-ESI-MS allowed for improved concentration sensitivity when detecting poorly responsive metabolites in complex biological samples without ionization suppression or isomeric/isobaric interferences. Method validation demonstrated that accurate yet precise quantification can be achieved for 20 different amino acid and acylcarnitine biomarkers associated with IEMs when using a single non-deuterated internal standard. CE-ESI-MS represents a promising second-tier method in newborn screening programs that is compatible with ESI-MS/MS technology in cases when improved specificity and sensitivity is warranted for diagnosis confirmation and subsequent monitoring.
authors.affiliation: Department of Chemistry, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S4M1, Canada.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chalcraft
authors.forename: Philip
authors.initials: P
authors.lastname: Britz-McKibbin
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D002138:Calibration; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D008403:Mass Screening / Q000379:methods; D008661:Metabolism, Inborn Errors / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000596:Amino Acids; C116917:acylcarnitine; D002331:Carnitine