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In Matrix Derivatization Combined with LC-MS/MS Results in Ultrasensitive Quantification of Plasma Free Metanephrines and Catecholamines

[Image: see text] Plasma-free metanephrines and catecholamines are essential markers in the biochemical diagnosis and follow-up of neuroendocrine tumors and inborn errors of metabolism. However, their low circulating concentrations (in the nanomolar range) and poor fragmentation characteristics hind...

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Autores principales: van Faassen, Martijn, Bischoff, Rainer, Eijkelenkamp, Karin, de Jong, Wilhelmina H. A., van der Ley, Claude P., Kema, Ido P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349590/
https://www.ncbi.nlm.nih.gov/pubmed/32484659
http://dx.doi.org/10.1021/acs.analchem.0c01263
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author van Faassen, Martijn
Bischoff, Rainer
Eijkelenkamp, Karin
de Jong, Wilhelmina H. A.
van der Ley, Claude P.
Kema, Ido P.
author_facet van Faassen, Martijn
Bischoff, Rainer
Eijkelenkamp, Karin
de Jong, Wilhelmina H. A.
van der Ley, Claude P.
Kema, Ido P.
author_sort van Faassen, Martijn
collection PubMed
description [Image: see text] Plasma-free metanephrines and catecholamines are essential markers in the biochemical diagnosis and follow-up of neuroendocrine tumors and inborn errors of metabolism. However, their low circulating concentrations (in the nanomolar range) and poor fragmentation characteristics hinder facile simultaneous quantification by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Here, we present a sensitive and simple matrix derivatization procedure using propionic anhydride that enables simultaneous quantification of unconjugated l-DOPA, catecholamines, and metanephrines in plasma by LC-MS/MS. Dilution of propionic anhydride 1:4 (v/v) in acetonitrile in combination with 50 μL of plasma resulted in the highest mass spectrometric response. In plasma, derivatization resulted in stable derivatives and increased sensitivity by a factor of 4–30 compared with a previous LC-MS/MS method for measuring plasma metanephrines in our laboratory. Furthermore, propionylation increased specificity, especially for 3-methoxytyramine, by preventing interference from antihypertensive medication (β-blockers). The method was validated according to international guidelines and correlated with a hydrophilic interaction LC-MS/MS method for measuring plasma metanephrines (R(2) > 0.99) and high-performance liquid chromatography with an electrochemical detection method for measuring plasma catecholamines (R(2) > 0.85). Reference intervals for l-DOPA, catecholamines, and metanephrines in n = 115 healthy individuals were established. Our work shows that analytes in the subnanomolar range in plasma can be derivatized in situ without any preceding sample extraction. The developed method shows improved sensitivity and selectivity over existing methods and enables simultaneous quantification of several classes of amines.
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spelling pubmed-73495902020-07-10 In Matrix Derivatization Combined with LC-MS/MS Results in Ultrasensitive Quantification of Plasma Free Metanephrines and Catecholamines van Faassen, Martijn Bischoff, Rainer Eijkelenkamp, Karin de Jong, Wilhelmina H. A. van der Ley, Claude P. Kema, Ido P. Anal Chem [Image: see text] Plasma-free metanephrines and catecholamines are essential markers in the biochemical diagnosis and follow-up of neuroendocrine tumors and inborn errors of metabolism. However, their low circulating concentrations (in the nanomolar range) and poor fragmentation characteristics hinder facile simultaneous quantification by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Here, we present a sensitive and simple matrix derivatization procedure using propionic anhydride that enables simultaneous quantification of unconjugated l-DOPA, catecholamines, and metanephrines in plasma by LC-MS/MS. Dilution of propionic anhydride 1:4 (v/v) in acetonitrile in combination with 50 μL of plasma resulted in the highest mass spectrometric response. In plasma, derivatization resulted in stable derivatives and increased sensitivity by a factor of 4–30 compared with a previous LC-MS/MS method for measuring plasma metanephrines in our laboratory. Furthermore, propionylation increased specificity, especially for 3-methoxytyramine, by preventing interference from antihypertensive medication (β-blockers). The method was validated according to international guidelines and correlated with a hydrophilic interaction LC-MS/MS method for measuring plasma metanephrines (R(2) > 0.99) and high-performance liquid chromatography with an electrochemical detection method for measuring plasma catecholamines (R(2) > 0.85). Reference intervals for l-DOPA, catecholamines, and metanephrines in n = 115 healthy individuals were established. Our work shows that analytes in the subnanomolar range in plasma can be derivatized in situ without any preceding sample extraction. The developed method shows improved sensitivity and selectivity over existing methods and enables simultaneous quantification of several classes of amines. American Chemical Society 2020-06-02 2020-07-07 /pmc/articles/PMC7349590/ /pubmed/32484659 http://dx.doi.org/10.1021/acs.analchem.0c01263 Text en Copyright © 2020 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle van Faassen, Martijn
Bischoff, Rainer
Eijkelenkamp, Karin
de Jong, Wilhelmina H. A.
van der Ley, Claude P.
Kema, Ido P.
In Matrix Derivatization Combined with LC-MS/MS Results in Ultrasensitive Quantification of Plasma Free Metanephrines and Catecholamines
title In Matrix Derivatization Combined with LC-MS/MS Results in Ultrasensitive Quantification of Plasma Free Metanephrines and Catecholamines
title_full In Matrix Derivatization Combined with LC-MS/MS Results in Ultrasensitive Quantification of Plasma Free Metanephrines and Catecholamines
title_fullStr In Matrix Derivatization Combined with LC-MS/MS Results in Ultrasensitive Quantification of Plasma Free Metanephrines and Catecholamines
title_full_unstemmed In Matrix Derivatization Combined with LC-MS/MS Results in Ultrasensitive Quantification of Plasma Free Metanephrines and Catecholamines
title_short In Matrix Derivatization Combined with LC-MS/MS Results in Ultrasensitive Quantification of Plasma Free Metanephrines and Catecholamines
title_sort in matrix derivatization combined with lc-ms/ms results in ultrasensitive quantification of plasma free metanephrines and catecholamines
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349590/
https://www.ncbi.nlm.nih.gov/pubmed/32484659
http://dx.doi.org/10.1021/acs.analchem.0c01263
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