2023 年 7 巻 1 号 p. 80-88
A specific and sensitive method for the analysis of 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) as endogenous amines obtained from biological samples is described. These compounds, processed by a combination of solvent and solid-phase extraction (SPE), have been analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The levels of TIQ and 1-MeTIQ in biological samples were determined with the aid of the deuterated internal standard (IS) 1-MeTIQ-d4 using multiple reaction monitoring (MRM, product ions m/z 90.9 of m/z 133.8 for TIQ, m/z 130.8 of m/z 147.8 for 1-MeTIQ and m/z 133.8 of m/z 151.8 for 1-MeTIQ-d4). The chromatographic separation was conducted on a reversed phase 5CN-MS column (150×2.0 mm, i.d.) using a mobile phase comprised of methanol and 5 mM ammonium formate (90 : 10, v/v) at a flow rate of 0.2 mL/min. The calibration curves for TIQ and 1-MeTIQ using 1-MeTIQ-d4 were linear (r2>0.99) in the selected concentration range for each compound. The lower limits of detection of each compound were 0.10 ng/mL for TIQ and 0.01 ng/mL for 1-MeTIQ. The good recoveries for TIQ (>93.2%) and 1-MeTIQ (>94.1%) in this assay precluded the need to concentrate samples prior to analysis. TIQ and 1-MeTIQ contents in mouse brains following intraperitoneal administration of haloperidol (HP) were measured, and TIQ content did not differ significantly from those in control group, but 1-MeTIQ content decreased significantly. This result agrees well previous findings in human parkinsonism and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse brain.