Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patients

In a recent untargeted clinical lipidomics study of platelets of coronary artery disease (CAD) patients, medium-chain phosphatidylcholines (MCPCs) with C8 and C10 fatty acyl residues were found significantly upregulated in the patient group with acute coronary syndrome (ACS) as compared to chronic c...

Full description

Saved in:
Bibliographic Details
Main Authors: Tamara Janker, Adrian Brun, Adrian Sievers-Engler, Kristina Dittrich, Meinrad Gawaz, Michael Lämmerhofer
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Journal of Chromatography Open
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2772391724000471
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850256805638176768
author Tamara Janker
Adrian Brun
Adrian Sievers-Engler
Kristina Dittrich
Meinrad Gawaz
Michael Lämmerhofer
author_facet Tamara Janker
Adrian Brun
Adrian Sievers-Engler
Kristina Dittrich
Meinrad Gawaz
Michael Lämmerhofer
author_sort Tamara Janker
collection DOAJ
description In a recent untargeted clinical lipidomics study of platelets of coronary artery disease (CAD) patients, medium-chain phosphatidylcholines (MCPCs) with C8 and C10 fatty acyl residues were found significantly upregulated in the patient group with acute coronary syndrome (ACS) as compared to chronic coronary syndrome (CCS) and healthy controls. To support this finding, this work presents the development and optimization of a targeted UHPLC-QTrap-MS/MS method with multiple reaction monitoring acquisition for the quantitative analysis of MCPCs (PC 10:0/8:0, PC 16:0/8:0, PC 10:0/20:4 and PC 10:0/10:0) in platelets for biomarker validation. A systematic optimization of chromatographic and mass spectrometric parameters was performed. A charged surface hybrid CSH C18 (1.7 µm, 130 Å) column and fine-tuned gradient elution with 2-propanol/acetonitrile and ammonium acetate as additive to the mobile phase was employed in the final method in ESI negative mode. Four selected PC standards (PC 6:0/6:0, PC 8:0/8:0, PC 10:0/10:0 and PC 12:0/12:0), which cover well the carbon and retention rime range of the target analytes, were used for the optimization process and calibration. Quantification was based on matrix-matched calibration with these four selected commercially available MCPC standards as surrogate calibrants and PC 6:0/6:0(d22) as internal standard. Furthermore, an organic solvent and fatty acyl carbon number-corrected response factor approach gave also accuracies within acceptance limits of bioanalytical validation guidelines and has more generic applicability. Compared to the previous untargeted RPLC-ESI-QTOF-MS/MS method, the optimized targeted UHPLC-QTrap-MS/MS assay showed increased sensitivity and selectivity for the detection of medium-chain PCs in platelet samples of CAD (LOQs in the range of 0.5–5 nmol/L). The method performance parameters indicated its suitability for a future biomarker validation study of MCPCs in platelets.
format Article
id doaj-art-7712b110674344cc8d6cc146eb3e16ee
institution OA Journals
issn 2772-3917
language English
publishDate 2024-11-01
publisher Elsevier
record_format Article
series Journal of Chromatography Open
spelling doaj-art-7712b110674344cc8d6cc146eb3e16ee2025-08-20T01:56:34ZengElsevierJournal of Chromatography Open2772-39172024-11-01610016010.1016/j.jcoa.2024.100160Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patientsTamara Janker0Adrian Brun1Adrian Sievers-Engler2Kristina Dittrich3Meinrad Gawaz4Michael Lämmerhofer5Pharmaceutical (Bio-)Analysis, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, GermanyPharmaceutical (Bio-)Analysis, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, GermanyPharmaceutical (Bio-)Analysis, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany; Corresponding authors. Pharmaceutical (Bio-)Analysis, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8 72076 Tuebingen, Germany.Pharmaceutical (Bio-)Analysis, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, GermanyDepartment of Cardiology and Angiology, University Hospital Tuebingen, Eberhard Karls University Tuebingen, Otfried-Mueller-Straße 10 72076 Tuebingen, GermanyPharmaceutical (Bio-)Analysis, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany; Corresponding authors. Pharmaceutical (Bio-)Analysis, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8 72076 Tuebingen, Germany.In a recent untargeted clinical lipidomics study of platelets of coronary artery disease (CAD) patients, medium-chain phosphatidylcholines (MCPCs) with C8 and C10 fatty acyl residues were found significantly upregulated in the patient group with acute coronary syndrome (ACS) as compared to chronic coronary syndrome (CCS) and healthy controls. To support this finding, this work presents the development and optimization of a targeted UHPLC-QTrap-MS/MS method with multiple reaction monitoring acquisition for the quantitative analysis of MCPCs (PC 10:0/8:0, PC 16:0/8:0, PC 10:0/20:4 and PC 10:0/10:0) in platelets for biomarker validation. A systematic optimization of chromatographic and mass spectrometric parameters was performed. A charged surface hybrid CSH C18 (1.7 µm, 130 Å) column and fine-tuned gradient elution with 2-propanol/acetonitrile and ammonium acetate as additive to the mobile phase was employed in the final method in ESI negative mode. Four selected PC standards (PC 6:0/6:0, PC 8:0/8:0, PC 10:0/10:0 and PC 12:0/12:0), which cover well the carbon and retention rime range of the target analytes, were used for the optimization process and calibration. Quantification was based on matrix-matched calibration with these four selected commercially available MCPC standards as surrogate calibrants and PC 6:0/6:0(d22) as internal standard. Furthermore, an organic solvent and fatty acyl carbon number-corrected response factor approach gave also accuracies within acceptance limits of bioanalytical validation guidelines and has more generic applicability. Compared to the previous untargeted RPLC-ESI-QTOF-MS/MS method, the optimized targeted UHPLC-QTrap-MS/MS assay showed increased sensitivity and selectivity for the detection of medium-chain PCs in platelet samples of CAD (LOQs in the range of 0.5–5 nmol/L). The method performance parameters indicated its suitability for a future biomarker validation study of MCPCs in platelets.http://www.sciencedirect.com/science/article/pii/S2772391724000471BiomarkerClinical lipidomicsMass spectrometryPhospholipidsAcute coronary syndrome
spellingShingle Tamara Janker
Adrian Brun
Adrian Sievers-Engler
Kristina Dittrich
Meinrad Gawaz
Michael Lämmerhofer
Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patients
Journal of Chromatography Open
Biomarker
Clinical lipidomics
Mass spectrometry
Phospholipids
Acute coronary syndrome
title Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patients
title_full Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patients
title_fullStr Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patients
title_full_unstemmed Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patients
title_short Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patients
title_sort targeted ultra high performance liquid chromatography tandem mass spectrometry assay for the quantification of medium chain phosphatidylcholines in platelets of coronary artery disease patients
topic Biomarker
Clinical lipidomics
Mass spectrometry
Phospholipids
Acute coronary syndrome
url http://www.sciencedirect.com/science/article/pii/S2772391724000471
work_keys_str_mv AT tamarajanker targetedultrahighperformanceliquidchromatographytandemmassspectrometryassayforthequantificationofmediumchainphosphatidylcholinesinplateletsofcoronaryarterydiseasepatients
AT adrianbrun targetedultrahighperformanceliquidchromatographytandemmassspectrometryassayforthequantificationofmediumchainphosphatidylcholinesinplateletsofcoronaryarterydiseasepatients
AT adriansieversengler targetedultrahighperformanceliquidchromatographytandemmassspectrometryassayforthequantificationofmediumchainphosphatidylcholinesinplateletsofcoronaryarterydiseasepatients
AT kristinadittrich targetedultrahighperformanceliquidchromatographytandemmassspectrometryassayforthequantificationofmediumchainphosphatidylcholinesinplateletsofcoronaryarterydiseasepatients
AT meinradgawaz targetedultrahighperformanceliquidchromatographytandemmassspectrometryassayforthequantificationofmediumchainphosphatidylcholinesinplateletsofcoronaryarterydiseasepatients
AT michaellammerhofer targetedultrahighperformanceliquidchromatographytandemmassspectrometryassayforthequantificationofmediumchainphosphatidylcholinesinplateletsofcoronaryarterydiseasepatients