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A UPLC-MRM-MS method for comprehensive profiling of Amadori compound-modified phosphatidylethanolamines in human plasma

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Abstract

Phosphatidylethanolamines (PEs) are targets of non-enzymatic glycation, a chemical process that occurs between glucose and primary amine-containing biomolecules. As the early-stage non-enzymatic glycation products of PE, Amadori-PEs are implicated in the pathogenesis of various diseases. However, only a few Amadori-PE molecular species have been identified so far; a comprehensive profiling of these glycated PE species is needed to establish their roles in disease pathology. Herein, based on our previous work using liquid chromatography-coupled neutral loss scanning and product ion scanning tandem mass spectrometry (LC-NLS-MS and LC-PIS-MS) in tandem, we extend identification of Amadori-PE to the low-abundance species, which is facilitated by using plasma lipids glycated in vitro. The confidence of identification is improved by high-resolution tandem mass spectrometry and chromatographic retention time regression. A LC-coupled multiple reaction monitoring mass spectrometry (LC-MRM-MS) assay is further developed for more sensitive quantitation of the Amadori compound-modified lipids. Using synthesized stable isotope-labeled Amadori lipids as internal standards, levels of 142 Amadori-PEs and 33 Amadori-LysoPEs are determined in the NIST human plasma standard reference material. These values may serve as an important reference for future investigations of Amadori-modified lipids in human diseases.

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Author notes

  1. Xiaobo He

    Present address: National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA

Authors and Affiliations

  1. Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA

    Xiaobo He, Zhucui Li & Qibin Zhang

  2. Department of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, 27412, USA

    Qibin Zhang

Authors
  1. Xiaobo He
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  2. Zhucui Li
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Correspondence to Qibin Zhang.

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De-identified, commercial human plasma was used in this work. Research conducted with unidentified samples is not considered human subjects research and is not regulated by the Federal Policy for the Protection of Human Subjects (45 CFR Part 46).

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He, X., Li, Z. & Zhang, Q. A UPLC-MRM-MS method for comprehensive profiling of Amadori compound-modified phosphatidylethanolamines in human plasma. Anal Bioanal Chem 413, 431–443 (2021). https://doi.org/10.1007/s00216-020-03012-w

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  • DOI: https://doi.org/10.1007/s00216-020-03012-w

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