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Sensitive mass spectrometric assay for determination of 15-deoxy-Δ(12,14)-prostaglandin J(2) and its application in human plasma samples of patients with diabetes
The determination of individual prostaglandins (PG) in humans is mainly performed in urine samples. The quantification of PGs in human plasma could improve the understanding of particular PG species under various physiological and pathological conditions. 15-Deoxy-Δ(12,14)-prostaglandin J(2) (15d-PG...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750338/ https://www.ncbi.nlm.nih.gov/pubmed/29143878 http://dx.doi.org/10.1007/s00216-017-0748-1 |
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author | Morgenstern, Jakob Fleming, Thomas Kadiyska, Ivelina Brings, Sebastian Groener, Jan Benedikt Nawroth, Peter Hecker, Markus Brune, Maik |
author_facet | Morgenstern, Jakob Fleming, Thomas Kadiyska, Ivelina Brings, Sebastian Groener, Jan Benedikt Nawroth, Peter Hecker, Markus Brune, Maik |
author_sort | Morgenstern, Jakob |
collection | PubMed |
description | The determination of individual prostaglandins (PG) in humans is mainly performed in urine samples. The quantification of PGs in human plasma could improve the understanding of particular PG species under various physiological and pathological conditions. 15-Deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a dehydrated downstream product of PGD(2) and is of high interest due to its recently discovered anti-inflammatory effects. Increasing availability of highly sensitive mass spectrometry allows the quantification of low abundant biomarkers like 15d-PGJ(2) in human plasma samples. Herein, a sensitive LC-MS/MS method for the determination of 15d-PGJ(2) was established. The method was validated according to the guidance of the American Food and Drug Administration and tested in plasma samples from patients with poorly controlled diabetes, considered to be a pro-inflammatory condition. Extraction of 15d-PGJ(2) was achieved with an easy-to-use liquid-liquid extraction by ethyl acetate following a methanol precipitation. The lower limit of quantification was 2.5 pg mL(−1) and linearity (R (2) = 0.998) was guaranteed between 2.5 and 500 pg mL(−1) for 15d-PGJ(2). Selectivity was assured by the use of two individual mass transitions (qualifier and quantifier). Precision and accuracy were validated in an inter- and intraday assay with a coefficient of variation below 11.8% (intraday) and 14.7% (interday). In diabetic patients with an HbA(1C) > 9%, increased plasma concentrations of 15d-PGJ(2) compared to control plasma were measured. 15d-PGJ(2) correlated negatively with the inflammation marker C-reactive protein. The developed LC-MS/MS method represents a new possibility to quantify 15d-PGJ(2) with high specificity in human plasma samples. This may contribute to a better understanding of the potential anti-inflammatory effects of 15d-PGJ(2) in severe long-term pro-inflammatory disorders like diabetes, cancer, or cardiovascular disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00216-017-0748-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5750338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-57503382018-01-22 Sensitive mass spectrometric assay for determination of 15-deoxy-Δ(12,14)-prostaglandin J(2) and its application in human plasma samples of patients with diabetes Morgenstern, Jakob Fleming, Thomas Kadiyska, Ivelina Brings, Sebastian Groener, Jan Benedikt Nawroth, Peter Hecker, Markus Brune, Maik Anal Bioanal Chem Research Paper The determination of individual prostaglandins (PG) in humans is mainly performed in urine samples. The quantification of PGs in human plasma could improve the understanding of particular PG species under various physiological and pathological conditions. 15-Deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a dehydrated downstream product of PGD(2) and is of high interest due to its recently discovered anti-inflammatory effects. Increasing availability of highly sensitive mass spectrometry allows the quantification of low abundant biomarkers like 15d-PGJ(2) in human plasma samples. Herein, a sensitive LC-MS/MS method for the determination of 15d-PGJ(2) was established. The method was validated according to the guidance of the American Food and Drug Administration and tested in plasma samples from patients with poorly controlled diabetes, considered to be a pro-inflammatory condition. Extraction of 15d-PGJ(2) was achieved with an easy-to-use liquid-liquid extraction by ethyl acetate following a methanol precipitation. The lower limit of quantification was 2.5 pg mL(−1) and linearity (R (2) = 0.998) was guaranteed between 2.5 and 500 pg mL(−1) for 15d-PGJ(2). Selectivity was assured by the use of two individual mass transitions (qualifier and quantifier). Precision and accuracy were validated in an inter- and intraday assay with a coefficient of variation below 11.8% (intraday) and 14.7% (interday). In diabetic patients with an HbA(1C) > 9%, increased plasma concentrations of 15d-PGJ(2) compared to control plasma were measured. 15d-PGJ(2) correlated negatively with the inflammation marker C-reactive protein. The developed LC-MS/MS method represents a new possibility to quantify 15d-PGJ(2) with high specificity in human plasma samples. This may contribute to a better understanding of the potential anti-inflammatory effects of 15d-PGJ(2) in severe long-term pro-inflammatory disorders like diabetes, cancer, or cardiovascular disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00216-017-0748-1) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2017-11-16 2018 /pmc/articles/PMC5750338/ /pubmed/29143878 http://dx.doi.org/10.1007/s00216-017-0748-1 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Paper Morgenstern, Jakob Fleming, Thomas Kadiyska, Ivelina Brings, Sebastian Groener, Jan Benedikt Nawroth, Peter Hecker, Markus Brune, Maik Sensitive mass spectrometric assay for determination of 15-deoxy-Δ(12,14)-prostaglandin J(2) and its application in human plasma samples of patients with diabetes |
title | Sensitive mass spectrometric assay for determination of 15-deoxy-Δ(12,14)-prostaglandin J(2) and its application in human plasma samples of patients with diabetes |
title_full | Sensitive mass spectrometric assay for determination of 15-deoxy-Δ(12,14)-prostaglandin J(2) and its application in human plasma samples of patients with diabetes |
title_fullStr | Sensitive mass spectrometric assay for determination of 15-deoxy-Δ(12,14)-prostaglandin J(2) and its application in human plasma samples of patients with diabetes |
title_full_unstemmed | Sensitive mass spectrometric assay for determination of 15-deoxy-Δ(12,14)-prostaglandin J(2) and its application in human plasma samples of patients with diabetes |
title_short | Sensitive mass spectrometric assay for determination of 15-deoxy-Δ(12,14)-prostaglandin J(2) and its application in human plasma samples of patients with diabetes |
title_sort | sensitive mass spectrometric assay for determination of 15-deoxy-δ(12,14)-prostaglandin j(2) and its application in human plasma samples of patients with diabetes |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750338/ https://www.ncbi.nlm.nih.gov/pubmed/29143878 http://dx.doi.org/10.1007/s00216-017-0748-1 |
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