Stable isotope gas chromatography–tandem mass spectrometry determination of aminoethylcysteine ketimine decarboxylated dimer in biological samples

Dimitrios Tsikas; Christopher E Evans; Travis T Denton; Anja Mitschke; Frank-Mathias Gutzki; John T Pinto; Tetyana Khomenko; Sandor Szabo; Arthur J.L Cooper

doi:10.1016/j.ab.2012.07.022

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Stable isotope gas chromatography–tandem mass spectrometry determination of aminoethylcysteine ketimine decarboxylated dimer in biological samples

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Stable isotope gas chromatography–tandem mass spectrometry determination of aminoethylcysteine ketimine decarboxylated dimer in biological samples

Dimitrios Tsikas, Christopher E Evans, Travis T Denton, Anja Mitschke, Frank-Mathias Gutzki, John T Pinto, Tetyana Khomenko, Sandor Szabo and Arthur J.L Cooper

Analytical biochemistry, Vol.430(1), pp.4-15

11/01/2012

DOI: https://doi.org/10.1016/j.ab.2012.07.022

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https://hdl.handle.net/2376/105236

PMID: 22858756

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Abstract

GC–MS/MS

Validation

Brain

Vegetables

Cysteamine

AECK–DD

Organic cation transporters

Aminoethylcysteine ketimine decarboxylated dimer (AECK–DD; systematic name: 1,2-3,4-5,6-7,8-octahydro-1,8a-diaza-4,6-dithiafluoren-9(8aH)-one) is a previously described metabolite of cysteamine that has been reported to be present in mammalian brain, urine, plasma, and cells in culture and vegetables and to possess potent antioxidative properties. Here, we describe a stable isotope gas chromatography–tandem mass spectrometry (GC–MS/MS) method for specific and sensitive determination of AECK–DD in biological samples. 13C2-labeled AECK–DD was synthesized and used as the internal standard. Derivatization was carried out by N-pentafluorobenzylation with pentafluorobenzyl bromide in acetonitrile. Quantification was performed by selected reaction monitoring of the mass transitions m/z 328 to 268 for AECK–DD and m/z 330 to 270 for [13C2]AECK–DD in the electron capture negative ion chemical ionization mode. The procedure was systematically validated for human plasma and urine samples. AECK–DD was not detectable in human plasma above approximately 4nM but was present in urine samples of healthy humans at a maximal concentration of 46nM. AECK–DD was detectable in rat brain at very low levels of approximately 8pmol/g wet weight. Higher levels of AECK–DD were detected in mouse brain (∼1nmol/g wet weight). Among nine dietary vegetables evaluated, only shallots were found to contain trace amounts of AECK–DD (∼6.8pmol/g fresh tissue).

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Title: Stable isotope gas chromatography–tandem mass spectrometry determination of aminoethylcysteine ketimine decarboxylated dimer in biological samples
Creators: Dimitrios Tsikas - Institute of Clinical Pharmacology, Hannover Medical School, 30625 Hannover, Germany
Christopher E Evans - Department of Chemistry and Biochemistry, Eastern Washington University, Cheney, WA 99004, USA
Travis T Denton - Department of Chemistry and Biochemistry, Eastern Washington University, Cheney, WA 99004, USA
Anja Mitschke - Institute of Clinical Pharmacology, Hannover Medical School, 30625 Hannover, Germany
Frank-Mathias Gutzki - Institute of Clinical Pharmacology, Hannover Medical School, 30625 Hannover, Germany
John T Pinto - Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA
Tetyana Khomenko - Departments of Pathology and Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA
Sandor Szabo - Departments of Pathology and Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA
Arthur J.L Cooper - Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA
Publication Details: Analytical biochemistry, Vol.430(1), pp.4-15
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: Elsevier Inc
Identifiers: 99900547092901842
Language: English
Resource Type: Journal article