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Direct analysis of dried blood spots by in-line desorption combined with high-resolution chromatography and mass spectrometry for quantification of maple syrup urine disease biomarkers leucine and isoleucine

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Abstract

A in-line desorption device was developed, which allows for direct analysis of dried blood spots eliminating the need for punching disks from the filter paper cards. Using this device, we have validated a method to quantify biomarkers related to maple syrup urine disease (MSUD), a metabolism disorder that often requires a second-tier test for confirmation. Direct analysis of newborn screening cards is conducted in-line with a high-resolution chromatographic separation with mass spectrometry using electrospray ionization and multiple-reaction monitoring. Quantification of leucine and isoleucine using an isotopically labeled internal standard encompasses a range suitable for MSUD assessment. Precision and accuracy of the technique was acceptable with relative standard deviations within 10% at three fortified concentrations and an unfortified level. A post-column infusion test shows minimum matrix suppression was observed using this direct sampling technique.

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Acknowledgments

Virginia Division of Consolidated Laboratory Services for internal standard reference material

Altria Client Services for fabrication of prototype device

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Authors and Affiliations

  1. Department of Pharmaceutics, Virginia Commonwealth University Medical Center, PO Box 980533, Richmond, VA, 23298-0533, USA

    John H. Miller IV & H. Thomas Karnes

  2. Division of Consolidated Laboratory Services (DCLS), Department of General Services, Commonwealth of Virginia, 600 North 5th Street, Richmond, VA, 23219-1439, USA

    Philip A. Poston

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  1. John H. Miller IV
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  2. Philip A. Poston
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Correspondence to John H. Miller IV.

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Miller, J.H., Poston, P.A. & Karnes, H.T. Direct analysis of dried blood spots by in-line desorption combined with high-resolution chromatography and mass spectrometry for quantification of maple syrup urine disease biomarkers leucine and isoleucine. Anal Bioanal Chem 400, 237–244 (2011). https://doi.org/10.1007/s00216-011-4740-x

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  • DOI: https://doi.org/10.1007/s00216-011-4740-x

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