Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction - Parallel Ion Parking.

Autor: Lin Y; Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32308, United States., Agarwal AM; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84108, United States., Anderson LC; Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32310, United States., Marshall AG; Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32308, United States.; Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32310, United States.
Jazyk: angličtina
Zdroj: Journal of mass spectrometry and advances in the clinical lab [J Mass Spectrom Adv Clin Lab] 2023 Feb 02; Vol. 28, pp. 20-26. Date of Electronic Publication: 2023 Feb 02 (Print Publication: 2023).
DOI: 10.1016/j.jmsacl.2023.01.004
Abstrakt: β-thalassemia is a quantitative hemoglobin (Hb) disorder resulting in reduced production of Hb A and increased levels of Hb A 2 . Diagnosis of β-thalassemia can be problematic when combined with other structural Hb variants, so that the separation approaches in routine clinical centers are not sufficiently decisive to obtain accurate results. Here, we separate the intact Hb subunits by high-performance liquid chromatography, followed by top-down tandem mass spectrometry of intact subunits to distinguish Hb variants. Proton transfer reaction-parallel ion parking (PTR-PIP), in which a radical anion removes protons from multiply charged precursor ions and produces charge-reduced ions spanning a limited m / z range, was used to increase the signal-to-noise ratio of the subunits of interest. We demonstrate that the δ/β ratio can act as a biomarker to identify β-thalassemia in normal electrospray ionization MS1 and PTR-PIP MS1. The application of PTR-PIP significantly increases the sensitivity and specificity of the HPLC-MS method to identify δ/β ratio as a thalassemia biomarker.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2023 THE AUTHORS. Publishing services by ELSEVIER B.V. on behalf of MSACL.)
Databáze: MEDLINE
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