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Metabolites
Volume 11
Issue 1
10.3390/metabo11010060
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Article

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

by
Jakob Morgenstern
1,*,
Thomas Fleming
1,2,
Elisabeth Kliemank
1,
Maik Brune
1,
Peter Nawroth
1 and
Andreas Fischer
1,3,4
1
Department of Internal Medicine I and Clinical Chemistry, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
2
German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
3
Division Vascular Signaling and Cancer (A270), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
4
European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
*
Author to whom correspondence should be addressed.
Metabolites 2021, 11(1), 60; https://doi.org/10.3390/metabo11010060
Submission received: 16 December 2020 / Revised: 12 January 2021 / Accepted: 15 January 2021 / Published: 19 January 2021
(This article belongs to the Section Advances in Metabolomics)
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Abstract

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 (atRA) 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 atRA in human plasma samples. The isolation of atRA 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−1, and 7 point calibration displayed good linearity (R2 = 0.994) in the range of 50–3200 pg mL−1. 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 atRA from hyperlipidemic samples. Applying this method to plasma samples from patients with poorly controlled Type 2 diabetes significantly decreased atRA plasma levels as compared to those of the healthy controls. In addition, atRA concentrations were highly associated with increased low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) cholesterol levels.
Keywords: retinoic acid; liquid chromatography–tandem mass spectrometry; hyperlipidemia; liquid–liquid extraction retinoic acid; liquid chromatography–tandem mass spectrometry; hyperlipidemia; liquid–liquid extraction

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MDPI and ACS Style

Morgenstern, J.; Fleming, T.; Kliemank, E.; Brune, M.; Nawroth, P.; Fischer, A. Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes. Metabolites 2021, 11, 60. https://doi.org/10.3390/metabo11010060

AMA Style

Morgenstern J, Fleming T, Kliemank E, Brune M, Nawroth P, Fischer A. Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes. Metabolites. 2021; 11(1):60. https://doi.org/10.3390/metabo11010060

Chicago/Turabian Style

Morgenstern, Jakob, Thomas Fleming, Elisabeth Kliemank, Maik Brune, Peter Nawroth, and Andreas Fischer. 2021. "Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes" Metabolites 11, no. 1: 60. https://doi.org/10.3390/metabo11010060

APA Style

Morgenstern, J., Fleming, T., Kliemank, E., Brune, M., Nawroth, P., & Fischer, A. (2021). Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes. Metabolites, 11(1), 60. https://doi.org/10.3390/metabo11010060

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