Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion Parking
β-thalassemia is a quantitative hemoglobin (Hb) disorder resulting in reduced production of Hb A and increased levels of Hb A2. 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 suffici...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Journal of Mass Spectrometry and Advances in the Clinical Lab |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667145X23000044 |
| _version_ | 1797829476499849216 |
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| author | Yuan Lin Archana M. Agarwal Lissa C. Anderson Alan G. Marshall |
| author_facet | Yuan Lin Archana M. Agarwal Lissa C. Anderson Alan G. Marshall |
| author_sort | Yuan Lin |
| collection | DOAJ |
| description | β-thalassemia is a quantitative hemoglobin (Hb) disorder resulting in reduced production of Hb A and increased levels of Hb A2. 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. |
| first_indexed | 2024-04-09T13:21:52Z |
| format | Article |
| id | doaj.art-443ff5a76964420f81ed8dc10a72db82 |
| institution | Directory Open Access Journal |
| issn | 2667-145X |
| language | English |
| last_indexed | 2024-04-09T13:21:52Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Mass Spectrometry and Advances in the Clinical Lab |
| spelling | doaj.art-443ff5a76964420f81ed8dc10a72db822023-05-11T04:24:59ZengElsevierJournal of Mass Spectrometry and Advances in the Clinical Lab2667-145X2023-04-01282026Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion ParkingYuan Lin0Archana M. Agarwal1Lissa C. Anderson2Alan G. Marshall3Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32308, United StatesDepartment 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 StatesIon Cyclotron Resonance Program, National High Magnetic Field Laboratory, 1800 E. Paul Dirac Drive, Tallahassee, FL 32310, United States; Corresponding authors at: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32308, United States (A.G. Marshall).Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32308, United States; Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, 1800 E. Paul Dirac Drive, Tallahassee, FL 32310, United States; Corresponding authors at: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32308, United States (A.G. Marshall).β-thalassemia is a quantitative hemoglobin (Hb) disorder resulting in reduced production of Hb A and increased levels of Hb A2. 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.http://www.sciencedirect.com/science/article/pii/S2667145X23000044Top-downFourier transform ion cyclotron resonanceFTMSFT-ICRδ/β ratio |
| spellingShingle | Yuan Lin Archana M. Agarwal Lissa C. Anderson Alan G. Marshall Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion Parking Journal of Mass Spectrometry and Advances in the Clinical Lab Top-down Fourier transform ion cyclotron resonance FTMS FT-ICR δ/β ratio |
| title | Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion Parking |
| title_full | Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion Parking |
| title_fullStr | Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion Parking |
| title_full_unstemmed | Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion Parking |
| title_short | Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion Parking |
| title_sort | discovery of a biomarker for β thalassemia by hplc ms and improvement from proton transfer reaction parallel ion parking |
| topic | Top-down Fourier transform ion cyclotron resonance FTMS FT-ICR δ/β ratio |
| url | http://www.sciencedirect.com/science/article/pii/S2667145X23000044 |
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