Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes

Retinoic acids are vitamin A metabolites that have numerous essential functions in humans, and are also used as drugs to treat acne and acute promyelocytic leukemia. All-trans retinoic acid (<i>at</i>RA) is the major occurring metabolite of retinoic acid in humans. This study provides a...

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Main Authors: Jakob Morgenstern, Thomas Fleming, Elisabeth Kliemank, Maik Brune, Peter Nawroth, Andreas Fischer
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/11/1/60
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author Jakob Morgenstern
Thomas Fleming
Elisabeth Kliemank
Maik Brune
Peter Nawroth
Andreas Fischer
author_facet Jakob Morgenstern
Thomas Fleming
Elisabeth Kliemank
Maik Brune
Peter Nawroth
Andreas Fischer
author_sort Jakob Morgenstern
collection DOAJ
description Retinoic acids are vitamin A metabolites that have numerous essential functions in humans, and are also used as drugs to treat acne and acute promyelocytic leukemia. All-trans retinoic acid (<i>at</i>RA) is the major occurring metabolite of retinoic acid in humans. This study provides a sensitive and specific liquid chromatography–tandem mass spectrometry approach in order to quantify <i>at</i>RA in human plasma samples. The isolation of <i>at</i>RA by hyperacidified liquid–liquid extraction using hexane and ethyl acetate resulted in a recovery of 89.7 ± 9.2%. The lower limit of detection was 20 pg·mL<sup>−1</sup>, and 7 point calibration displayed good linearity (R<sup>2</sup> = 0.994) in the range of 50–3200 pg mL<sup>−1</sup>. Selectivity was guaranteed by the use of two individual mass transitions (qualifier and quantifier), and precision and accuracy were determined intraday and interday with a coefficient variation of 9.3% (intraday) and 14.0% (interday). Moreover, the method could be used to isolate <i>at</i>RA from hyperlipidemic samples. Applying this method to plasma samples from patients with poorly controlled Type 2 diabetes significantly decreased <i>at</i>RA plasma levels as compared to those of the healthy controls. In addition, <i>at</i>RA concentrations were highly associated with increased low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) cholesterol levels.
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spelling doaj.art-965415ec9526423593bc28e3338cb46b2023-12-03T13:52:16ZengMDPI AGMetabolites2218-19892021-01-011116010.3390/metabo11010060Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 DiabetesJakob Morgenstern0Thomas Fleming1Elisabeth Kliemank2Maik Brune3Peter Nawroth4Andreas Fischer5Department of Internal Medicine I and Clinical Chemistry, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment of Internal Medicine I and Clinical Chemistry, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment of Internal Medicine I and Clinical Chemistry, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment of Internal Medicine I and Clinical Chemistry, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment of Internal Medicine I and Clinical Chemistry, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment of Internal Medicine I and Clinical Chemistry, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyRetinoic acids are vitamin A metabolites that have numerous essential functions in humans, and are also used as drugs to treat acne and acute promyelocytic leukemia. All-trans retinoic acid (<i>at</i>RA) is the major occurring metabolite of retinoic acid in humans. This study provides a sensitive and specific liquid chromatography–tandem mass spectrometry approach in order to quantify <i>at</i>RA in human plasma samples. The isolation of <i>at</i>RA by hyperacidified liquid–liquid extraction using hexane and ethyl acetate resulted in a recovery of 89.7 ± 9.2%. The lower limit of detection was 20 pg·mL<sup>−1</sup>, and 7 point calibration displayed good linearity (R<sup>2</sup> = 0.994) in the range of 50–3200 pg mL<sup>−1</sup>. Selectivity was guaranteed by the use of two individual mass transitions (qualifier and quantifier), and precision and accuracy were determined intraday and interday with a coefficient variation of 9.3% (intraday) and 14.0% (interday). Moreover, the method could be used to isolate <i>at</i>RA from hyperlipidemic samples. Applying this method to plasma samples from patients with poorly controlled Type 2 diabetes significantly decreased <i>at</i>RA plasma levels as compared to those of the healthy controls. In addition, <i>at</i>RA concentrations were highly associated with increased low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) cholesterol levels.https://www.mdpi.com/2218-1989/11/1/60retinoic acidliquid chromatography–tandem mass spectrometryhyperlipidemialiquid–liquid extraction
spellingShingle Jakob Morgenstern
Thomas Fleming
Elisabeth Kliemank
Maik Brune
Peter Nawroth
Andreas Fischer
Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes
Metabolites
retinoic acid
liquid chromatography–tandem mass spectrometry
hyperlipidemia
liquid–liquid extraction
title Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes
title_full Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes
title_fullStr Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes
title_full_unstemmed Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes
title_short Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes
title_sort quantification of all trans retinoic acid by liquid chromatography tandem mass spectrometry and association with lipid profile in patients with type 2 diabetes
topic retinoic acid
liquid chromatography–tandem mass spectrometry
hyperlipidemia
liquid–liquid extraction
url https://www.mdpi.com/2218-1989/11/1/60
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