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Updated: Aug 5, 2026
10:17
High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
Improving the Throughput and Specificity for Small-Molecule Analysis During First-Tier Mass Spectrometry-Based
Samantha L Isenberg1, Charles A Pickens1, Rachel Lee1
1Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
Metabolites
|July 27, 2026
Summary
New mass spectrometry methods significantly boost newborn screening throughput and specificity. These advancements in flow injection analysis tandem mass spectrometry (FIA-MS/MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) improve early disease detection.
Area of Science:
- Clinical Chemistry and Mass Spectrometry
- Biomarker Discovery and Analysis
- Newborn Screening Technologies
Background:
- Current newborn screening relies on rapid, less specific first-tier assays, often requiring slower, more specific second-tier tests.
- Stagnant throughput and specificity of first-tier assays limit the ability to screen for an expanding number of disorders.
- Need for higher-throughput and more specific assays in newborn screening laboratories is critical.
Purpose of the Study:
- To develop and evaluate novel first-tier tandem mass spectrometry assays for newborn screening.
- To enhance assay throughput and analytical specificity using a modern LC-MS/MS platform.
- To assess the performance of a rapid flow injection analysis tandem mass spectrometry (FIA-MS/MS) and a hydrophilic interaction chromatography (HILIC) guard column LC-MS/MS assay.
Main Methods:
- Developed and tested two first-tier tandem mass spectrometry methods on a dual-needle, dual-loop LC-MS/MS system.
- Assayed a 30-second FIA-MS/MS method for increased throughput.
- Evaluated a rapid LC-MS/MS method using a HILIC guard column (1TH) for improved specificity, assessing recovery, precision, linearity, and matrix effects.
Main Results:
- The 30-second FIA-MS/MS assay quadrupled the throughput of existing 2-minute assays.
- The 1TH LC-MS/MS method successfully separated critical isobaric and isomeric biomarkers, reducing matrix effects.
- The 1TH LC-MS/MS method demonstrated improved specificity and quantification accuracy while maintaining acceptable analytical performance for newborn screening.
Conclusions:
- Advances in LC-MS/MS instrumentation enable substantial increases in newborn screening throughput or improved analytical specificity.
- First-tier LC-MS/MS with a HILIC guard column enhances specificity, potentially reducing the need for second-tier testing.
- These methods offer flexible solutions for expanding newborn screening panels without compromising quality or efficiency.
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