Development and validation of a highly-sensitive, quantitative LC-MS/MS assay to evaluate plasma oxytocin

Introduction: Oxytocin is a 9-amino acid peptide that serves as neuromodulator in the human central nervous system. This peptide is implicated in the regulation of diverse behaviors and plays a significant role in positive social interaction. Currently, oxytocin levels are measured using immunoassay...

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Main Authors: E. Grifnée, A. Mackowiak, J. Demeuse, M. Schoumacher, L. Huyghebaert, W. Determe, T. Dubrowski, P. Massonnet, S. Peeters, G. Scantamburlo, E. Cavalier, C.Le Goff
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Journal of Mass Spectrometry and Advances in the Clinical Lab
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667145X25000057
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author E. Grifnée
A. Mackowiak
J. Demeuse
M. Schoumacher
L. Huyghebaert
W. Determe
T. Dubrowski
P. Massonnet
S. Peeters
G. Scantamburlo
E. Cavalier
C.Le Goff
author_facet E. Grifnée
A. Mackowiak
J. Demeuse
M. Schoumacher
L. Huyghebaert
W. Determe
T. Dubrowski
P. Massonnet
S. Peeters
G. Scantamburlo
E. Cavalier
C.Le Goff
author_sort E. Grifnée
collection DOAJ
description Introduction: Oxytocin is a 9-amino acid peptide that serves as neuromodulator in the human central nervous system. This peptide is implicated in the regulation of diverse behaviors and plays a significant role in positive social interaction. Currently, oxytocin levels are measured using immunoassays. However, these methods have several limitations that can lead to false results and erroneous interpretation. Given the remarkably low endogenous level of oxytocin in human plasma (low ng/L levels), we developed and rigorously validated a novel and highly sensitive LC-MS/MS method for oxytocin quantification in plasma. Methods: Oxytocin was initially extracted using solid-phase extraction with an Oasis HLB 30 mg plate and then subjected to LC-MS/MS analysis. PBS-0.1 % BSA served as surrogate matrix for the preparation of validation samples and the calibration curve, ensuring no endogenous interference. The validation design followed the Clinical Laboratory Standards Institute guidelines. Precision, accuracy, and measurement uncertainty were determined using single-nested analysis of variance and e.noval software. Results: A lower limit of quantification of 1 ng/L was achieved. The method was validated for oxytocin concentrations ranging from 1 ng/L to 75 ng/L, with precision (coefficient of variation) below 10 %, accuracy ranging from 94 % to 108 %, and measurement uncertainty below 15 %. Conclusion: In this work, we developed and validated a highly sensitive LC-MS/MS method for the quantification of oxytocin in plasma. Our novel methodology is well-suited for clinical applications.
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spelling doaj-art-8b35935f0ecf431fbe3a08fcf4ba55762025-08-20T02:28:19ZengElsevierJournal of Mass Spectrometry and Advances in the Clinical Lab2667-145X2025-04-0136192810.1016/j.jmsacl.2025.02.002Development and validation of a highly-sensitive, quantitative LC-MS/MS assay to evaluate plasma oxytocinE. Grifnée0A. Mackowiak1J. Demeuse2M. Schoumacher3L. Huyghebaert4W. Determe5T. Dubrowski6P. Massonnet7S. Peeters8G. Scantamburlo9E. Cavalier10C.Le Goff11Department of Clinical Chemistry, University Hospital of Liège, Belgium; Corresponding author.Department of Clinical Chemistry, University Hospital of Liège, BelgiumDepartment of Clinical Chemistry, CIRM, University of Liège, BelgiumDepartment of Clinical Chemistry, CIRM, University of Liège, BelgiumDepartment of Clinical Chemistry, University Hospital of Liège, BelgiumDepartment of Clinical Chemistry, CIRM, University of Liège, BelgiumDepartment of Clinical Chemistry, University Hospital of Liège, BelgiumDepartment of Clinical Chemistry, University Hospital of Liège, BelgiumDepartment of Clinical Chemistry, University Hospital of Liège, BelgiumDepartment of Psychiatry, University Hospital of Liège, BelgiumDepartment of Clinical Chemistry, University Hospital of Liège, Belgium; Department of Clinical Chemistry, CIRM, University of Liège, BelgiumDepartment of Clinical Chemistry, University Hospital of Liège, Belgium; Department of Clinical Chemistry, CIRM, University of Liège, BelgiumIntroduction: Oxytocin is a 9-amino acid peptide that serves as neuromodulator in the human central nervous system. This peptide is implicated in the regulation of diverse behaviors and plays a significant role in positive social interaction. Currently, oxytocin levels are measured using immunoassays. However, these methods have several limitations that can lead to false results and erroneous interpretation. Given the remarkably low endogenous level of oxytocin in human plasma (low ng/L levels), we developed and rigorously validated a novel and highly sensitive LC-MS/MS method for oxytocin quantification in plasma. Methods: Oxytocin was initially extracted using solid-phase extraction with an Oasis HLB 30 mg plate and then subjected to LC-MS/MS analysis. PBS-0.1 % BSA served as surrogate matrix for the preparation of validation samples and the calibration curve, ensuring no endogenous interference. The validation design followed the Clinical Laboratory Standards Institute guidelines. Precision, accuracy, and measurement uncertainty were determined using single-nested analysis of variance and e.noval software. Results: A lower limit of quantification of 1 ng/L was achieved. The method was validated for oxytocin concentrations ranging from 1 ng/L to 75 ng/L, with precision (coefficient of variation) below 10 %, accuracy ranging from 94 % to 108 %, and measurement uncertainty below 15 %. Conclusion: In this work, we developed and validated a highly sensitive LC-MS/MS method for the quantification of oxytocin in plasma. Our novel methodology is well-suited for clinical applications.http://www.sciencedirect.com/science/article/pii/S2667145X25000057OxytocinSolid phase extractionLiquid chromatographyTandem mass spectrometryCLSI guidelinesPsychiatric disorders
spellingShingle E. Grifnée
A. Mackowiak
J. Demeuse
M. Schoumacher
L. Huyghebaert
W. Determe
T. Dubrowski
P. Massonnet
S. Peeters
G. Scantamburlo
E. Cavalier
C.Le Goff
Development and validation of a highly-sensitive, quantitative LC-MS/MS assay to evaluate plasma oxytocin
Journal of Mass Spectrometry and Advances in the Clinical Lab
Oxytocin
Solid phase extraction
Liquid chromatography
Tandem mass spectrometry
CLSI guidelines
Psychiatric disorders
title Development and validation of a highly-sensitive, quantitative LC-MS/MS assay to evaluate plasma oxytocin
title_full Development and validation of a highly-sensitive, quantitative LC-MS/MS assay to evaluate plasma oxytocin
title_fullStr Development and validation of a highly-sensitive, quantitative LC-MS/MS assay to evaluate plasma oxytocin
title_full_unstemmed Development and validation of a highly-sensitive, quantitative LC-MS/MS assay to evaluate plasma oxytocin
title_short Development and validation of a highly-sensitive, quantitative LC-MS/MS assay to evaluate plasma oxytocin
title_sort development and validation of a highly sensitive quantitative lc ms ms assay to evaluate plasma oxytocin
topic Oxytocin
Solid phase extraction
Liquid chromatography
Tandem mass spectrometry
CLSI guidelines
Psychiatric disorders
url http://www.sciencedirect.com/science/article/pii/S2667145X25000057
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