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 microL injected) were effectively stacked and cleaned up in-line on a capillary column (5 cm x 0.25 mm I.D.) packed with 5 microm 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.
Song
Yaru
Y
Department of Chemistry, Jackson State University, 1400 Lynch Street, Jackson, MS 39217, USA.
Xu
Jianping
J
Hamme
Ashton
A
Liu
Yi-Ming
YM
D000818:Animals; D001812:Blood-Brain Barrier / Q000737:chemistry*; D001923:Brain Chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D015314:Dialysis Solutions / Q000032:analysis; D008297:Male; D009498:Neurotoxins / Q000032:analysis* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D044005:Tetrahydroisoquinolines / Q000032:analysis* / Q000378:metabolism*
D015314:Dialysis Solutions; D009498:Neurotoxins; D044005:Tetrahydroisoquinolines