Determination of Endogenous Neurotoxin 1-Acetyl-6,7-Dihydroxyl-1,2,3,4-Tetrahydroisoquinoline in Rat Substantia Nigra by High Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry

Abstract

The endogenous neurotoxin, 1-acetyl-6,7-dihydroxyl-1,2,3,4 –tetrahydro isoquinoline (ADTIQ), is acatecholamine isoquinoline, indicating its possible involvement in Parkinson's disease. Moreover, it has been assumed to be a bridge between diabetes and Parkinson's disease because metabolic synthesis resembles glucose metabolism. Therefore, the accurate determination of ADTIQ could play an important role in diagnosis of diabetes and Parkinson's disease. Herein, a sensitive and precise method was established to determine ADTIQ by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry in multiple reaction monitoring mode. The [M+H]⁺ precursor product ions for ADTIQ were 208.1/190.1 and linear range of calibration curve was from 1.0 to 250.0 nM. The limit of detection and limit of quantification of the developed method were 0.2 nM and 1 nM, respectively. The inter-day, intra-day precision, accuracy, and recoveries were acceptable for biological samples. Furthermore, the reported method was used to determine ADTIQ levels in the substantia nigra of rats. The results indicated that the developed method was highly sensitive and accurate for the determination of ADTIQ.

Keywords:

• 1-Acetyl-6,7-dihydroxyl-1,2,3,4-tetrahydroisoquinoline
• LC-MS/MS
• Liquid chromatography
• Mass spectrometry

Acknowledgments

Bingjie Xie, Yan Xiong, and Kaleem Ullah contributed equally to this work.

This work was supported by the National Science and Technology of China (the 11th five-year plan key projects, 2009BAK59B03) and National Basic Research Program of China (973 program, 2012CB91063).