title: Determination of the penetration of 9-fluoropropyl-(+)-dihydrotetrabenazine across the blood-brain barrier in rats by microdialysis combined with liquid chromatography-tandem mass spectrometry.
abstract: To evaluate the penetration of the blood-brain barrier by 9-fluoropropyl-(+)-dihydrotetrabenazine (AV-133), microdialysis probes were implanted simultaneously into rat blood and brain, and a liquid chromatography-tandem mass spectrometric method was developed and validated to monitor the AV-133 concentration in the microdialysates. The chromatographic separation was performed on an XTerra C(18) column (150 mm × 2.1 mm i.d., 5 μm particles) with gradient elution. The mass spectrometer was operated in positive mode using electrospray ionization. The analytes were measured using the multiple-reaction-monitoring mode. The calibration curves were linear over the range of 5.00-1000 ng/mL AV-133, with a coefficient of determination >0.995. The accuracies ranged from 99.5% to 105.0% and the precisions were <10% for AV-133. This method was used to determine the concentrations of AV-133 and its pharmacokinetics in the brains and blood of rats. The blood and brain concentration-time profiles for AV-133 were obtained, and the blood-brain barrier penetration was evaluated.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.forename: Jinping
authors.initials: J
authors.lastname: Qiao
authors.forename: Wei
authors.initials: W
authors.lastname: Yin
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003287:Contrast Media / Q000032:analysis* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D008297:Male; D017551:Microdialysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics
chemical_list: D003287:Contrast Media; D005462:Fluorine Radioisotopes; C549477:florbenazine F 18; D013747:Tetrabenazine