Capillary liquid chromatography–tandem mass spectrometry of tetrahydroisoquinoline derived neurotoxins: A study on the blood–brain barrier of rat brain

Certain tetrahydroisoquinoline derivatives such as 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-BnTIQ) and N-methylsalsolinol are parkinsonian neurotoxins. This paper describes a sensitive and reliable analytical method based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) for the determination of tetrahydroisoquinoline derivatives (TIQs) in brain dialysate. Samples (20 μL injected) were effectively stacked and cleaned up in-line on a capillary column (5 cm × 0.25 mm I.D.) packed with 5 μm phenyl reversed-phase silica particles. Under the optimized conditions, electrospray ionisation–MS/MS detection of TIQs was highly sensitive. The capillary LC–MS/MS method had a detection limit of 2 ng/ml for TIQ. The method was used in combination with in vivo microdialysis to study the blood–brain barrier (BBB) for TIQs. The microdialysis probe was implanted in the frontal cortex of rat brain. Test compounds were administered intraperitoneally (i.p.). Four TIQs including 1,2,3,4-tetrahydroisoquinoline (TIQ), 5,6,7,8-tetrahydroisoquinoline (5-TIQ), 1-BnTIQ, and salsolinol (SAL) were studied. A concentration maximum was detected in brain dialysate for TIQ, 5-TIQ, and 1-BnTIQ about 40 min after drug administration. However, SAL, the precursor of N-methylsalsolinol was found unable to cross the BBB of rat brain.