Quantitative Determination of Endogenous Tetrahydroisoquinolines, Potential Parkinson's Disease Biomarkers, in Mammals

ACS Chem Neurosci. 2022 Dec 7;13(23):3230-3246. doi: 10.1021/acschemneuro.2c00516. Epub 2022 Nov 14.


Current diagnostic options for Parkinson's disease are very limited and primarily based on characteristic clinical symptoms. Thus, there are urgent needs for reliable biomarkers that enable us to diagnose the disease in the early stages, differentiate it from other atypical Parkinsonian syndromes, monitor its progression, increase knowledge of its pathogenesis, and improve the development of potent therapies. A promising group of potential biomarkers are endogenous tetrahydroisoquinoline metabolites, which are thought to contribute to the multifactorial etiology of Parkinson's disease. The aim of this critical review is to highlight trends and limitations of available traditional and modern analytical techniques for sample pretreatment (extraction and derivatization procedures) and quantitative determination of tetrahydroisoquinoline derivatives in various types of mammalian fluids and tissues (urine, plasma, cerebrospinal fluid, brain tissue, liver tissue). Particular attention is paid to the most sensitive and specific analytical techniques, involving immunochemistry and gas or liquid chromatography coupled with mass spectrometric, fluorescence, or electrochemical detection. The review also includes a discussion of other relevant agents proposed and tested in Parkinson's disease.

Keywords: Tetrahydroisoquinolines; biomarker; fluids; mammals; quantitative analysis; tissues.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Humans
  • Parkinson Disease* / diagnosis
  • Tetrahydroisoquinolines* / analysis


  • Biomarkers
  • Tetrahydroisoquinolines