Analytical and Bioanalytical Chemistry

, Volume 409, Issue 23, pp 5501–5512 | Cite as

Urinary profiling of tryptophan and its related metabolites in patients with metabolic syndrome by liquid chromatography-electrospray ionization/mass spectrometry

  • Ji Sun Oh
  • Hong Seong Seo
  • Kyoung Heon Kim
  • Heesoo Pyo
  • Bong Chul Chung
  • Jeongae LeeEmail author
Research Paper


Tryptophan (Trp) is an essential amino acid that plays an important role in protein synthesis and is a precursor of various substances related to diverse biological functions. An imbalance in Trp metabolites is associated with inflammatory diseases. The accurate and precise measurement of these compounds in biological specimens would provide meaningful information for understanding the biochemical states of various metabolic syndrome-related diseases, such as hyperlipidemia, hypertension, diabetes, and obesity. In this study, we developed a rapid, accurate, and sensitive liquid chromatography-tandem mass spectrometry-based method for the simultaneous targeted analysis of Trp and its related metabolites of the kynurenine (Kyn), serotonin, and tryptamine pathways in urine. The application of the developed method was tested using urine samples after protein precipitation. The detection limits of Trp and its metabolites were in the range of 0.01 to 0.1 μg/mL. The method was successfully validated and applied to urine samples from controls and patients with metabolic syndrome. Our results revealed high concentrations of Kyn, kynurenic acid, xanthurenic acid, and quinolinic acid as well as a high Kyn-to-Trp ratio (KTR) in patients with metabolic syndromes. The levels of urine Kyn and KTR were significantly increased in patients under 60 years old. The profiling of urinary Trp metabolites could be a useful indicator for age-related diseases including metabolic syndrome.


LC-MS Urinary tryptophan metabolites Kynurenine pathway Metabolic syndrome 



3-Hydroxyanthranilic acid












5-Hyroxyindole-3-acetic acid






Anthranilic acid




Gas chromatography


High-performance liquid chromatography


Indoleamine 2,3-dioxygenase enzymes


Kynurenic acid


Kyn-to-Trp ratio










Tandem mass spectrometry










Quinolinic acid






Tryptophan dioxygenase






Ultraviolet detector


Xanthurenic acid





This research was supported by the Bio & Medical Technology Development Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (NRF-2013M3A9B6046413) and by an intramural grant from the Korea Institute of Science and Technology (KIST).

Compliance with ethical standards

The experimental protocol (KUGH-12118-005) was approved by the Institutional Review Board Committee of the Human Research Protection Center at the College of Medicine, Korea University, and written informed consent was obtained from all participants in compliance with the principles of the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2017_486_MOESM1_ESM.pdf (104 kb)
ESM 1 (PDF 104 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Molecular Recognition Research CenterKorea Institute of Science and TechnologySeoulRepublic of Korea
  2. 2.Department of Biotechnology, Graduate SchoolKorea UniversitySeoulRepublic of Korea
  3. 3.Cardiovascular CenterKorea University Guro HospitalSeoulRepublic of Korea

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