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Occurrence of 2-methylthiazolidine-4-carboxylic acid, a condensation product of cysteine and acetaldehyde, in human blood as a consequence of ethanol consumption

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Abstract

Acetaldehyde is a strongly electrophilic compound that is endogenously produced as a first intermediate in oxidative ethanol metabolism. Its high reactivity towards biogenic nucleophiles has toxicity as a consequence. Acetaldehyde readily undergoes a non-enzymatic condensation reaction and consecutive ring formation with cysteine to form 2-methylthiazolidine-4-carboxylic acid (MTCA). For analytical purposes, N-acetylation of MTCA was required for stabilization and to enable its quantification by reversed-phase chromatography combined with electrospray ionization–tandem mass spectrometry. Qualitative screening of post mortem blood samples with negative blood alcohol concentration (BAC) mostly showed low basal levels of MTCA. In BAC-positive post mortem samples, but not in corresponding urine specimens, strongly increased levels were present. To estimate the association between ethanol consumption and the occurrence of MTCA in human blood, the time curves of BAC and MTCA concentration were determined after a single oral dose of 0.5 g ethanol per kilogram of body weight. The blood elimination kinetics of MTCA was slower than that of ethanol. The peak concentration of MTCA (12.6 mg L-1) was observed 4 h after ethanol intake (BAC 0.07‰) and MTCA was still detectable after 13 h. Although intermediary acetaldehyde scavenging by formation of MTCA is interesting from a toxicological point of view, lack of hydrolytic stability under physiological conditions may hamper the use of MTCA as a quantitative marker of acetaldehyde exposure, such as resulting from alcohol consumption.

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Author notes

  1. Wolfgang Bicker

    Present address: FTC-Forensic-Toxicological Laboratory Ltd., Gaudenzdorfer Gürtel 43-45, 1120, Vienna, Austria

Authors and Affiliations

  1. Department of Analytical Chemistry, University of Vienna, Währinger Strasse 38, 1090, Vienna, Austria

    Roland J. Reischl, Wolfgang Bicker, Günther Lamprecht & Wolfgang Lindner

  2. IFFB Department of Forensic Medicine and Forensic Neuropsychiatry, University of Salzburg, Ignaz-Harrer-Strasse 79, 5020, Salzburg, Austria

    Thomas Keller

Authors
  1. Roland J. Reischl
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  2. Wolfgang Bicker
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  3. Thomas Keller
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  4. Günther Lamprecht
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  5. Wolfgang Lindner
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Corresponding authors

Correspondence to Wolfgang Bicker or Wolfgang Lindner.

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Reischl, R.J., Bicker, W., Keller, T. et al. Occurrence of 2-methylthiazolidine-4-carboxylic acid, a condensation product of cysteine and acetaldehyde, in human blood as a consequence of ethanol consumption. Anal Bioanal Chem 404, 1779–1787 (2012). https://doi.org/10.1007/s00216-012-6255-5

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  • DOI: https://doi.org/10.1007/s00216-012-6255-5

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