Newborn screening of inborn errors of metabolism by capillary electrophoresis-electrospray ionization-mass spectrometry: a second-tier method with improved specificity and sensitivity

Anal Chem. 2009 Jan 1;81(1):307-14. doi: 10.1021/ac8020455.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acids / blood
  • Calibration
  • Carnitine / analogs & derivatives
  • Carnitine / blood
  • Electrophoresis, Capillary / methods*
  • Humans
  • Infant, Newborn
  • Mass Screening / methods
  • Metabolism, Inborn Errors / blood*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Spectrometry, Mass, Electrospray Ionization / methods*


  • Amino Acids
  • acylcarnitine
  • Carnitine